Neurohormonal and metabolic effects of severe and moderate salt restriction in non-obese normotensive adults. Effects of sodium salts on plasma renin activity and norepinephrine response to orthostasis in salt-sensitive normotensive subjects. Sodium sensitivity in essential hypertension: role of the renin-angiotensin-aldosterone system and predictive value of an intravenous frusemide test. Divergent hemodynamic and hormonal responses to varying salt intake in normotensive subjects. Effects of moderate sodium restriction on clinic and twenty-four-hour ambulatory blood pressure in elderly hypertensive subjects. Effects of dietary sodium reduction on blood pressure in subjects with resistant hypertension: results from a randomized trial. Normal renal tubular response to changes of sodium intake in hypertensive man. Normal responses of atrial natriuretic factor and renal tubular function to sodium loading in hypertension-prone humans. Metabolic and orthostatic blood pressure responses to a low-sodium diet in elderly hypertensives. Moderate salt restriction effectively lowers blood pressure and degree of salt sensitivity is related to baseline concentration of renin and N-terminal atrial natriuretic peptide in plasma. A randomized crossover study to compare the blood pressure response to sodium loading with and without chloride in patients with essential hypertension. Sodium chloride raises blood pressure in normotensive subjects. The study of sodium and blood pressure. Salt sensitivity in normotensives with and salt resistance in normotensives without heredity of hypertension. "Salt-sensitive" essential hypertension in men. Is the sodium ion alone important? Salt restriction among hypertensive patients: modest blood pressure effect and no adverse effects. Blood pressure and metabolic responses to moderate sodium restriction in isradipine-treated hypertensive patients. Effect of modest salt reduction on blood pressure, urinary albumin, and pulse wave velocity in white, black, and Asian mild hypertensives. Effects of dietary sodium on blood pressure in IDDM patients with nephropathy. Sodium restriction and blood pressure in hypertensive type II diabetics: randomised blind controlled and crossover studies of moderate sodium restriction and sodium supplementation. Blood-pressure response to moderate sodium restriction and to potassium supplementation in mild essential hypertension. The Hypertension Prevention Trial: three-year effects of dietary changes on blood pressure. Hypertension Prevention Trial Research Group. Effects of sodium intake on the pressor and renal responses to nitric oxide synthesis inhibition in normotensive individuals with different sodium sensitivity. Relationship between salt and blood pressure in hypertensive patients on chronic ACE-inhibition. Renin predicts diastolic blood pressure response to nonpharmacologic and pharmacologic therapy. Effect of dietary change on the return of hypertension after withdrawal of prolonged antihypertensive therapy (DISH). Dietary Intervention Study of Hypertension. Behaviour of adrenomedullin during acute and chronic salt loading in normotensive and hypertensive subjects. Dietary sodium affects systemic and renal hemodynamic response to NO inhibition in healthy humans. Metabolic effects of strict salt restriction in essential hypertensive patients. The effects of nonpharmacologic interventions on blood pressure of persons with high normal levels. Results of the Trials of Hypertension Prevention, Phase I. Effects of weight loss and sodium reduction intervention on blood pressure and hypertension incidence in overweight people with high-normal blood pressure. The Trials of Hypertension Prevention, phase II. The Trials of Hypertension Prevention Collaborative Research Group. Sodium reduction and weight loss in the treatment of hypertension in older persons: a randomized controlled trial of nonpharmacologic interventions in the elderly (TONE). TONE Collaborative Research Group. Effect of low vs. high dietary sodium on blood pressure levels in a normotensive Indo-Asian population. Parental history of hypertension, sodium loading, and cardiovascular response to stress. Glomerular filtration rate and blood pressure are unchanged by increased sodium intake in atorvastatin-treated healthy men. Salt-sensitivity testing in patients with borderline hypertension: reproducibility and potential mechanisms. [Metabolic effects of changes in dietary sodium intake in patients with essential hypertension]. Hemodynamic and neuroendocrine responses to changes in sodium intake in compensated heart failure. Evaluation of the effectiveness of a low sodium diet in the treatment of mild to moderate hypertension. Dietary sodium restriction: adverse effect on plasma lipids. Effects of reduced sodium intake on hypertension control in older individuals: results from the Trial of Nonpharmacologic Interventions in the Elderly (TONE). Double-blind randomised trial of modest salt restriction in older people. Sodium restriction can delay the return of hypertension in patients previously well-controlled on drug therapy. Effects of high- and low-sodium diets on ambulatory blood pressure in patients with hypertension receiving aliskiren. BP changes in obese hypertensive subjects during rapid weight loss. Comparison of restricted v unchanged salt intake. Exercise tolerance in the heat on low and normal salt intakes. Sodium restriction and potassium supplementation in young people with mildly elevated blood pressure. Effect of dietary counselling on blood pressure and arterial plasma catecholamines in primary hypertension. Sodium restriction in hypertensive patients treated with a converting enzyme inhibitor and a thiazide. Effects on left ventricular hypertrophy of long-term nonpharmacological treatment with sodium restriction in mild-to-moderate essential hypertension. Response of diastolic blood pressure to long-term sodium restriction is posture related. Effects of moderate salt restriction alone and in combination with cilazapril on office and ambulatory blood pressure. Sodium intake alters the effects of norepinephrine on blood pressure. Adrenergic activity and peripheral hemodynamics in relation to sodium sensitivity in patients with essential hypertension. Dietary salt produces abnormal renal vasoconstrictor responses to upright posture in borderline hypertensive subjects. Plasma ouabain-like factor during acute and chronic changes in sodium balance in essential hypertension. Reduction in blood pressure with a low sodium, high potassium, high magnesium salt in older subjects with mild to moderate hypertension. Blood pressure reductions with exercise and sodium restriction in postmenopausal women with elevated systolic pressure: role of arterial stiffness. The 24 h blood pressure responses of hypertensives to a once-a-day cilazapril regimen. [Effect of moderate salt restriction on the antihypertensive action of nifedipine: a double blind study]. Effects of a new oral contraceptive containing an antimineralocorticoid progestogen, drospirenone, on the renin-aldosterone system, body weight, blood pressure, glucose tolerance, and lipid metabolism. The effect of ACE inhibitor and angiotensin II receptor antagonist therapy on serum uric acid levels and potassium homeostasis in hypertensive renal transplant recipients treated with CsA. Renal functional response to protein loading in type 1 (insulin-dependent) diabetic patients on normal or high salt intake. Double-blind randomised crossover trial of moderate sodium restriction in essential hypertension. Effect of dietary sodium intake on blood lipids: results from the DASH-sodium trial. Adjunctive effect of salt restriction on antihypertensive efficacy. Serial changes in blood pressure, renal function, endothelin and lipoprotein (a) during the first 9 days of cyclosporin therapy in males. Active kallikrein response to changes in sodium-chloride intake in essential hypertensive patients. Enhanced responsiveness of blood pressure to sodium intake and to angiotensin II is associated with insulin resistance in IDDM patients with microalbuminuria. Glucose load and renal sodium handling in mild essential hypertension on different sodium intakes. Effects of atorvastatin on red-blood cell Na(+)/Li(+) countertransport in hyperlipidemic patients with and without hypertension. Modest salt reduction reduces blood pressure and urine protein excretion in black hypertensives: a randomized control trial. Controlled trial of long term oral potassium supplements in patients with mild hypertension. Blood pressure is linked to salt intake and modulated by the angiotensinogen gene in normotensive and hypertensive elderly subjects. Effects of adding spironolactone to an angiotensin-converting enzyme inhibitor in chronic congestive heart failure secondary to coronary artery disease. Salt restriction: effects on lipids and insulin production in hypertensive patients. Cardiac secretion and renal clearance of atrial natriuretic peptide in normal man: effect of salt restriction. Dietary sodium restriction rapidly improves large elastic artery compliance in older adults with systolic hypertension. Effect of sodium intake on insulin sensitivity. Dietary sodium restriction impairs insulin sensitivity in noninsulin-dependent diabetes mellitus. Effect of sodium nitroprusside on mortality in acute myocardial infarction. Salt-induced increases in systolic blood pressure affect renal hemodynamics and proteinuria. Two-way factorial study of alcohol and salt restriction in treated hypertensive men. [Effect of an oral calcium supplement in the treatment of slight-to- moderate essential arterial hypertension]. Effects of a low-salt diet and of acute salt loading on blood pressure and intralymphocytic sodium concentration in young subjects with borderline hypertension. Deficiency of renal dopaminergic-dependent natriuretic response to acute sodium load in black salt-sensitive subjects in contrast to salt-resistant subjects. Nitric oxide production decreases after salt loading but is not related to blood pressure changes or nitric oxide-mediated vascular responses. Comparison of once-daily, niacin extended-release/lovastatin with standard doses of atorvastatin and simvastatin (the ADvicor Versus Other Cholesterol-Modulating Agents Trial Evaluation [ADVOCATE]). Effect of fosinopril in children with steroid-resistant idiopathic nephrotic syndrome. Moderate dietary salt restriction does not alter insulin resistance or serum lipids in normal men. Low-dose continuous infusion of human atrial natriuretic peptide during and after cardiac surgery. Cardiopulmonary effects of 7.2% saline solution compared with gelatin infusion in the early postoperative period after coronary artery bypass grafting. Arterial effects of salt restriction in hypertensive patients. A 9-week, randomized, double-blind, crossover study. A randomized trial on sodium reduction in two developing countries. Serum lipid changes on low salt diet. Effects of alpha 1-adrenergic blockade. Effects on blood pressure of reduced dietary sodium and the Dietary Approaches to Stop Hypertension (DASH) diet. DASH-Sodium Collaborative Research Group. Cyclosporine-induced hypertension and decline in renal function in healthy volunteers. Antihypertensive effect of enalapril as first-step treatment of mild and moderate uncomplicated essential hypertension. Evaluation by two methods of blood pressure measurement. Atorvastatin: an effective lipid-modifying agent in familial hypercholesterolemia. Effect of hypertonic saline dextran on acid-base balance in patients undergoing surgery of abdominal aortic aneurysm. Decreased insulin sensitivity during dietary sodium restriction is not mediated by effects of angiotensin II on insulin action.
The effects of severe and moderate sodium restriction on blood pressure, neurohormonal activity and serum lipids were studied in non-obese normotensive adults.
                In the first part of the study, 163 subjects were randomly assigned to a diet of 20 or 300 mmol/day sodium for 1 week each. In the second part, 25 subjects were given a diet of 85 or 200 mmol/day sodium for 4 weeks each in random order.
                After severe salt restriction 19% of the subjects had a significant decline (salt-sensitive group), 15% showed a significant rise (counter-regulator group) and 66% exhibited no change in blood pressure (salt-resistant group). Severe sodium restriction increased plasma renin activity and noradrenaline concentration, as well as serum total and low-density lipoprotein-cholesterol and triglycerides. After correction for haematocrit, only the changes in total and low-density lipoprotein-cholesterol remained significant. The rise in plasma renin activity during salt restriction was steeper in the counter-regulator group than in the other groups, whereas the changes in plasma noradrenaline concentrations were similar in all groups. During moderate salt restriction, plasma renin activity and noradrenaline concentration were significantly increased, but serum lipid concentrations and blood pressure did not change.
                In non-obese normotensive adults, severe and moderate salt restriction stimulates neurohormonal activity. In contrast to severe salt restriction, a moderate reduction in dietary salt intake does not influence blood lipids in normotensive subjects. The blood pressure-raising effect of sodium chloride in salt-sensitive individuals depends on the administration of both sodium and chloride. While sodium chloride is well known to suppress the activity of the renin-angiotensin-aldosterone and the sympathetic nervous system, the effects of nonchloride sodium salts on the response of these systems to physiological stimuli have not been previously studied. We therefore examined the effect of dietary intake of sodium chloride or sodium citrate on the activity of the renin-angiotensin-aldosterone and the sympathetic nervous system during rest and following stimulation by active orthostasis in normotensive salt-sensitive (n = 7) and salt-resistant (n = 8) subjects. The subjects were given a low-salt diet (20 mmol/day) for 3 weeks, to which a supplement of 200 mmol sodium per day, provided as either sodium chloride or sodium citrate, or a placebo, was added for 1 week each. We found that sodium chloride raised blood pressure in the salt-sensitive subjects (P < .005), while sodium citrate did not. Both salts, however, led to a similar suppression of the plasma levels of renin activity, angiotensin II, aldosterone, and norepinephrine (P < .01). Both sodium salts attenuated the renin response to orthostasis in salt-sensitive and salt-resistant individuals (P < .01), but the orthostasis-induced rise in renin activity was significantly smaller in the salt-sensitive than in the salt-resistant group under both sodium salts (P < .05).(ABSTRACT TRUNCATED AT 250 WORDS) In order to determine factors contributing to sodium induced changes of blood pressure, 20 patients with essential hypertension were studied when on their regular sodium intake and after two weeks of a low sodium diet (50 mmol daily) and two weeks of a high sodium diet (300 mmol daily). There were two periods of regular sodium intake, one of four weeks at the beginning and one of two weeks at the end of the study. The change in mean arterial pressure between the high and low salt diets (delta MAP) was regarded as a measure of sodium sensitivity, and was directly correlated with age and initial blood pressure. Compared with non-responders, responders (delta MAP 10 mmHg or more) showed a lesser activation of the renin-angiotensin-aldosterone system during the low salt period. The response to the administration of intravenous frusemide was not helpful in predicting sodium sensitivity. A significant but relatively small (4.2 mmHg) reduction in MAP was obtained during low salt period compared with the first period of regular sodium intake. The data suggest that moderate dietary sodium restriction can help to reduce the blood pressure of the relatively older patient with hypertension. Blood pressure responses to 1 week of low-salt (20 mmol sodium/d) and high-salt (300 mmol sodium/d) intake were investigated in a single-blind randomized study in 163 white, nonobese normotensive subjects (65 women and 98 men; mean age, 38 +/- 1.2 years). The individuals were classified as salt sensitive when mean arterial blood pressure rose by at least 5 mm Hg during high-salt intake, as salt resistant when mean arterial blood pressure changed by less than 5 mm Hg, and as "counterregulator" when mean arterial blood pressure fell by at least 5 mm Hg during the high-salt diet. Reexamination of 31 subjects showed that this approach to the testing of salt sensitivity was reliable and reproducible. Thirty subjects (18.4%) were classified as salt sensitive, 108 (66.3%) as salt resistant, and 25 (15.3%) as counterregulators. Multiple regression analysis revealed that age, body weight, and family history of hypertension contributed significantly to the change in blood pressure after the diets. Salt sensitivity was more frequent in older subjects and in those with a positive family history of hypertension. An increase in blood pressure after salt restriction was more likely in younger individuals and in those with a negative family history of hypertension. Plasma renin activity and plasma aldosterone concentrations were lower in salt-sensitive compared with salt-resistant and counterregulating subjects. The rise in plasma renin activity during salt restriction was most pronounced in counterregulating subjects. Plasma norepinephrine concentrations were not different among the groups.(ABSTRACT TRUNCATED AT 250 WORDS) To assess the effects of 80 mmol/day reduction in dietary sodium intake on clinic and 24-h ambulatory blood pressure in elderly hypertensive subjects.
                Double-blind, randomized, placebo-controlled, crossover trial lasting 10 weeks, following a 4-week run-in period.
                Seventeen untreated subjects with essential hypertension [systolic blood pressure (SBP) > or = 160 mmHg and/or diastolic blood pressure (DBP) > or = 95 mmHg], mean age 73 years (range 66-79).
                Subjects had clinic blood pressure and 24-h urinary electrolyte excretion measured while on their normal diet. Following a 4-week run-in period on a reduced-sodium diet (80-100 mmol/24 h) subjects entered a 10-week crossover trial of 80 mmol/24 h sodium supplement or matching placebo while continuing on the reduced-sodium diet.
                The within-patient change in clinic and 24-h ambulatory blood pressures at the end of each intervention period.
                Mean urinary sodium excretion at the end of the run-in phase rose during the high sodium intake phase and was reduced significantly at the end of the low sodium intake phase. There was a significant reduction in clinic supine SBP between the high- and low-sodium phases. There was no significant change in standing SBP, supine or standing DBP or pulse rate between phases. There was a non-significant reduction in mean 24-h SBP and DBP on the low sodium intake. At the end of the low-sodium phase there was a significant increase in plasma renin activity and aldosterone levels, but no change in plasma electrolytes.
                Overall, moderate sodium restriction in elderly hypertensives resulted in a significant fall in clinic supine SBP only, although marked differences in intersubject responses were found. Moderate sodium restriction may be of benefit in only some elderly hypertensive subjects as part of a non-pharmacological regimen for blood pressure reduction. Observational studies indicate a significant relation between dietary sodium and level of blood pressure. However, the role of salt sensitivity in the development of resistant hypertension is unknown. The present study examined the effects of dietary salt restriction on office and 24-hour ambulatory blood pressure in subjects with resistant hypertension. Twelve subjects with resistant hypertension entered into a randomized crossover evaluation of low (50 mmol/24 hours x 7 days) and high sodium diets (250 mmol/24 hours x 7 days) separated by a 2-week washout period. Brain natriuretic peptide; plasma renin activity; 24-hour urinary aldosterone, sodium, and potassium; 24-hour ambulatory blood pressure monitoring; aortic pulse wave velocity; and augmentation index were compared between dietary treatment periods. At baseline, subjects were on an average of 3.4+/-0.5 antihypertensive medications with a mean office BP of 145.8+/-10.8/83.9+/-11.2 mm Hg. Mean urinary sodium excretion was 46.1+/-26.8 versus 252.2+/-64.6 mmol/24 hours during low- versus high-salt intake. Low- compared to high-salt diet decreased office systolic and diastolic blood pressure by 22.7 and 9.1 mm Hg, respectively. Plasma renin activity increased whereas brain natriuretic peptide and creatinine clearance decreased during low-salt intake, indicative of intravascular volume reduction. These results indicate that excessive dietary sodium ingestion contributes importantly to resistance to antihypertensive treatment. Strategies to substantially reduce dietary salt intake should be part of the overall treatment of resistant hypertension. In a comparative study the influence of changes in dietary sodium intake on blood pressure, renal function, extracellular fluid volume, the renin-angiotensin-aldosterone system and plasma concentrations of arginine vasopressin, atrial natriuretic factor and cyclic guanosine monophosphate (GMP) was investigated in 12 patients with essential hypertension and in 10 normotensive controls. The subjects were studied after 4 days on a low (50 mmol/day), medium (180 mmol/day) or high (380 mmol/day) sodium intake. Renal sodium handling was assessed by simultaneous measurements of 51Cr-ethylenediaminetetraacetic acid (EDTA), lithium and sodium clearances. Identical values for the extracellular fluid volume, glomerular filtration rate and proximal and distal tubular resorption rates of sodium and water were found in the hypertensive patients and the controls at all three levels of sodium intake. In both groups, raising the sodium intake from low to high significantly increased 51Cr-EDTA and lithium clearance (an indirect measure of end-proximal fluid delivery), with intermediate values for the medium-sodium diet. The estimated values of fractional proximal and distal sodium resorption decreased when sodium intake was raised; the absolute proximal sodium resorption rate did not change, whereas the absolute distal sodium resorption rate as well as the extracellular fluid volume and sodium clearance increased. Blood pressure and the heart rate were unaffected by sodium intake. In both hypertensives and controls, plasma concentrations of active renin, angiotensin II and aldosterone decreased with increasing sodium intake, arginine vasopressin did not change, and atrial natriuretic factor and cyclic GMP increased.(ABSTRACT TRUNCATED AT 250 WORDS) In order to explore the hypothesis of an atrial natriuretic factor (ANF) deficiency in prehypertension, we compared the response to sodium loading on ANF and renal function in subjects with positive and negative histories of hypertension.
                Twenty-two offspring of hypertensive parents (OH) and 20 offspring of normotensive parents (ON) were studied after 4 days of low (50 mmol/day) or high (300 mmol/day) dietary sodium intake. The diets were allocated randomly. Blood pressure (BP), renal function, plasma concentration of ANF, cyclic guanosine monophosphate (cGMP), renin, angiotensin I and II, aldosterone, endothelin and catecholamines were determined during a clearance period of 90 min on both diets. Neurohormones were measured by radioimmunoassays. Renal function was determined by simultaneous measurements of 51Cr-ethylenediaminetetraacetate (a marker of glomerular filtration rate), lithium and sodium clearances.
                Supine systolic and diastolic BPs were significantly elevated in OH, with both low and high dietary sodium intake. There was no difference in ANF and cGMP concentrations on the low sodium diet. Increasing sodium intake caused a similar increase in ANF in OH and ON but cGMP did not change significantly. As expected the activity of the renin-angiotensin-aldosterone system was decreased by enhancing sodium intake but with both low and high sodium intake plasma renin concentration was significantly higher in OH than in ON. Activation of the sympathetic nervous system with low sodium intake was indicated by a moderate increase in plasma concentrations of epinephrine and norepinephrine in both groups. The renal effects were characterized by significant increases in GFR, lithium and sodium clearances with increasing sodium intake. There were no differences between OH and ON. Estimated values of fractional proximal and distal tubular sodium reabsorption decreased significantly and in a similar way in both OH and ON.
                These results indicate that the renal and neuroendocrine responses to dietary sodium loading are similar in both OH and ON. The only difference was a higher BP and an elevated plasma renin concentration on both dietary regimens in OH compared with ON. In particular, in OH and ON an identical increase in plasma ANF concentration in response to sodium loading was found. Thus, this study cannot support the hypothesis of a dysregulation of ANF in hypertension-prone humans. In view of the concern regarding the potential risks and benefits of sodium restriction, the effect on biochemical and orthostatic responses from a moderate reduction in sodium intake in elderly persons that is sufficient to lower systolic blood pressure (SBP) was examined. Seventeen hypertensive subjects aged 65-79 years entered a double-blind randomized placebo controlled cross-over trial of a low sodium diet plus placebo tablets vs a low sodium diet plus sodium tablets (80 mmols/day) each for 5 weeks. At the end of high and low sodium periods, two 24-h urine collections and venous blood samples were undertaken and supine and standing BPs were recorded. On the low compared to the high sodium phase (urinary sodium excretion 95 +/- 36 vs 174 +/- 40 mmols/24-h, respectively), clinic supine SBP fell by 8 mm Hg (95% CI: 1-15 mm Hg, P< 0.05) and diastolic BP (DBP) by 1 mm Hg (CI: -3 to 5 mm Hg); there was no change in total LDL- and HDL-cholesterol and triglyceride levels, serum calcium, phosphate, parathyroid hormone, glucose, creatinine clearance or urinary albumin excretion rate. Serum urate was significantly higher during the low compared to high sodium intake (304 +/- 56 vs 277 +/- 44 micromols/l). Orthostatic BP responses during the high and low sodium intakes were unchanged. In summary, after 5 weeks of moderate sodium restriction no adverse effects other than an increase in serum urate was seen in elderly hypertensive persons. The effect of salt restriction on blood pressure is under intense debate. We tested the effect of 100 mmol salt reduction on ambulatory blood pressure (ABP) in 46 Swedish individuals, 39 of whom completed the study, using a double-blind, placebo-controlled, cross-over design. Furthermore, we tested whether the basal plasma concentration of renin or N-terminal atrial natriuretic peptide (Nt-proANP) predict the degree of salt sensitivity.
                Participants received all meals and drinks with a total daily NaCl content of 50 mmol during 8 weeks. In addition, NaCl capsules (100 mmol/day) and corresponding placebo capsules were administered for 4 weeks each in random order. ABP after high-salt intake (150 mmol/day) was compared with ABP after low-salt intake (50 mmol/day). Salt sensitivity was defined as the difference between 24-h systolic ABP at the high-salt versus the low-salt periods. Baseline renin and Nt-proANP were related to salt sensitivity.
                Lowering of salt intake from 150 to 50 mmol/day induced significant blood pressure reductions (mean reduction, 95% confidence interval) in systolic and diastolic 24-h ABP (5.8, 3.4-8.2 and 2.6, 0.91-4.4 mmHg), daytime ABP (5.5, 2.9-8.1 and 2.3, 0.42-4.1 mmHg) and night-time ABP (6.4, 3.5-9.3 and 3.4, 1.4-5.5 mmHg). Baseline ln(renin) correlated inversely with salt sensitivity (r = -0.50, P = 0.001) whereas baseline ln(Nt-proANP) correlated directly (r = 0.33, P = 0.04).
                Lowering of salt intake with 100 mmol/day induces clinically relevant ABP reductions. Renin and Nt-proANP, measured with individuals on their habitual diet, could be useful biomarkers to identify individuals with the greatest blood pressure-lowering benefit from reduced salt intake. Six patients with essential hypertension underwent a randomized cross over design study to investigate the effect of supplementing a 10 mmol/day sodium diet for a period of 5 days with either 120 mmol sodium chloride (Slow Sodium, Ciba, Horsham, UK) or 122 mmol sodium in the presence of other anions, mainly phosphate (Phosphate, Sandoz, Feltham, UK). With both sodium salts, urinary sodium excretion was increased. The calculated amount of sodium retained was similar for both the sodium chloride and sodium phosphate periods. However, with the addition of sodium chloride to the low-salt diet, there were increases in supine mean blood pressure whereas with the addition of sodium phosphate no change in mean blood pressure occurred. The supine mean blood pressure after supplementation with sodium chloride (119.8 +/- 4.3 mmHg) was significantly greater than that after sodium phosphate (113.3 +/- 4.5 mmHg), similarly, the standing mean blood pressure was greater after addition of sodium chloride than of sodium phosphate (122.3 +/- 4.20 versus 115.4 +/- 3.0 mmHg). With both salts there were similar but non-significant increases in weight and reductions in plasma renin activity (PRA) and plasma aldosterone (PA). The effects of dietary sodium on blood pressure in normotensive adults is not well characterized. The Study of Sodium and Blood Pressure (SNaP) is a randomized, double-blind crossover trial using a placebo or 96 meq sodium in 4-week treatment periods separated by a 2-week washout period. Before capsule treatment periods, participants were instructed in a low sodium diet for 10 weeks to reduce urinary sodium excretion to less than 35 meq/8 hr. The low sodium diet was continued throughout the capsule treatment periods. Participants (n = 48; 47 white, 1 black) were 79% male and had an average age of 52 years, a body mass index of 27.6, and a baseline blood pressure of 131/84 mm Hg. Baseline overnight urinary sodium excretion was 51 meq/8 hr and 19 meq/8 hr after the low sodium diet run-in period, before the capsule treatment periods began. Resting, seated blood pressure was measured twice at each visit in a standard fashion. Differences between sodium and placebo treatment periods were as follows: systolic blood pressure, 123.9 versus 120.3 mm Hg, respectively (p less than 0.001); diastolic blood pressure, 78.7 versus 76.4 mm Hg, respectively (p = 0.005); and sodium excretion, 51.3 versus 30.9 meq/8 hr, respectively (p less than 0.001). Both systolic and diastolic blood pressures increased significant amounts in normotensive adults on a low sodium diet supplemented with 96 meq/day sodium. Long-term effects and dose-response relations need further study. We have studied blood pressure responses to moderate sodium restriction from 200 to 50 mmol/day over 2 weeks in 62 normotensive subjects with and without a family history of hypertension by continuous automatic blood pressure recording. Based on the average of the blood pressure of 1 hour continuous monitoring under basal conditions, we have been able to demonstrate a significant fall of blood pressure in 28 young subjects with a heredity of hypertension after moderate sodium restriction from 200 to 50 mmol over 2 weeks (fall in systolic blood pressure 5.4 +/- 1.1, diastolic 2.5 +/- 0.8, mean blood pressure 2.9 +/- 0.7 mmHg, mean +/- SEM), whereas blood pressure remained unchanged in a group of 34 subjects without heredity of hypertension after moderate sodium restriction (change in systolic blood pressure -1.0 +/- 0.6, diastolic blood pressure -0.6 +/- 0.7 and mean blood pressure -0.93 +/- 0.67 mmHg). 29 of the subjects were studied a third time 2 weeks after having returned to their usual high sodium diet and in those in whom a blood pressure fall was observed during sodium restriction it returned to pre-intervention values. This demonstrates that normotensives with a heredity of hypertension are salt sensitive and adds further evidence that a high sodium intake may be of critical importance for the initiation of essential hypertension. We investigated whether the anionic component of an orally administered sodium salt can influence the salt's capacity to increase blood pressure. In five men with essential hypertension in whom blood pressure was normal with restriction of dietary sodium chloride to 10 mmol per day (0.23 g of sodium per day), oral administration of sodium chloride for seven days, 240 mmol per day (5.52 g of sodium per day), induced significant increases in systolic and diastolic blood pressures, of 16 +/- 2 and 8 +/- 2 mm Hg (mean +/- SEM), respectively (P less than 0.05). An equimolar amount of sodium given as sodium citrate induced no change in blood pressure. Replacing supplemental sodium chloride with an equimolar amount of sodium as sodium citrate abolished the increase in blood pressure induced by sodium chloride. Both salts induced substantial and comparable sodium retention, weight gain, and suppression of plasma renin activity and plasma aldosterone, but supplemental sodium chloride increased plasma volume and urinary excretion of calcium, whereas sodium citrate did not. These preliminary findings demonstrate that the anionic component of an orally administered sodium salt can influence the ability of that salt to increase blood pressure, possibly by determining whether the salt induces an increase in plasma volume. Our observations in a small group of men with salt-sensitive hypertension will require confirmation in larger numbers of patients of both sexes. Previous studies, mainly evaluating short-term very low salt diets, suggest that salt restriction may influence glucose and insulin metabolism, catecholamines, renin, aldosterone, and lipid levels adversely. The authors wanted to explore whether sodium restriction for eight weeks influenced insulin secretion unfavourably, and evaluate the efficacy and safety of such treatment also in terms of other parameters important in the management of hypertensive patients.
                A double-blind randomized controlled parallel group designed trial. All participants received dietary advice aimed at a moderate salt-restricted diet. Half of the participants received salt capsules, the others received identical placebo capsules.
                General practice.
                Forty-six hypertensive patients inadequately controlled by drug treatment.
                Fasting serum insulin C-peptide and glucose and levels of these measures after oral glucose, blood pressure, serum aldosterone and lipids, peripheral resistance, and skin conductance.
                Salt restriction did not influence glucose and insulin metabolism, aldosterone, or lipid levels adversely. We observed better blood pressure regulation in the low salt group than in the high salt group, with a systolic and diastolic blood pressure difference of 5/5 mmHg after eight weeks. The difference was only statistically significant for diastolic blood pressure, p 0.02.
                This study revealed a modest diastolic blood pressure reducing effect of moderate sodium restriction. This reduction was obtained without any apparent unfavourable side effects such as increased insulin secretion, impaired glucose tolerance or dyslipidaemia. This multicenter, randomized, controlled clinical trial assessed the influence of sodium chloride intake on the antihypertensive effect of the calcium channel blocker isradipine. Participants with uncomplicated hypertension controlled by isradipine entered a 4-week sodium-restricted (60 to 80 mmol/24 h) period. Participants with urinary sodium levels < 120 mmol/24 h (n = 99) were randomized to placebo or sodium chloride (100 mmol/24 h) for 4 weeks, and then crossed over to the alternative treatment for an additional 4 weeks. Mean baseline systolic blood pressure was 151.9 +/- 16.7 mm Hg (mean +/- SD). During open-label isradipine treatment, systolic blood pressures for ad libitum sodium chloride and restriction were 134.1 +/- 11.1 and 132.1 +/- 12.2 mm Hg respectively; for double-blind sodium chloride restriction and supplementation: 133.6 +/- 12.6 and 138.5 +/- 12.8 mm Hg (P < .01). Urinary sodium excretion values for open-label isradipine ad libitum versus restricted were 140.6 +/- 61.9 versus 76.9 +/- 32.4 mmol/24 h; for double-blind restricted versus supplemented, sodium excretion was 120.5 +/- 68.9 v 175.9 +/- 68.7 mmol/24 h (P < or = .0001). Changes in urinary sodium excretion were not predictive of variations in blood pressure. Urinary sodium excretion during sodium restriction correlated directly with HDL-cholesterol (P < .02) and inversely with total cholesterol:HDL-cholesterol (P = .02), despite decreased total and saturated fat intake (P < .01). Sodium restriction was associated with significant reductions (P < .01) in virtually all macronutrients and electrolytes, and thus had an adverse impact on overall nutrition. The antihypertensive action of isradipine was not enhanced by dietary sodium chloride restriction, and the lipoprotein profile was least favorable with sodium chloride restriction. A reduction in salt intake lowers blood pressure. However, most previous trials were in whites with few in blacks and Asians. Salt reduction may also reduce other cardiovascular risk factors (eg, urinary albumin excretion, arterial stiffness). However, few well-controlled trials have studied these effects. We carried out a randomized double-blind crossover trial of salt restriction with slow sodium or placebo, each for 6 weeks, in 71 whites, 69 blacks, and 29 Asians with untreated mildly raised blood pressure. From slow sodium to placebo, urinary sodium was reduced from 165+/-58 (+/-SD) to 110+/-49 mmol/24 hours (9.7 to 6.5 g/d salt). With this reduction in salt intake, there was a significant decrease in blood pressure from 146+/-13/91+/-8 to 141+/-12/88+/-9 mm Hg (P<0.001), urinary albumin from 10.2 (IQR: 6.8 to 18.9) to 9.1 (6.6 to 14.0) mg/24 hours (P<0.001), albumin/creatinine ratio from 0.81 (0.47 to 1.43) to 0.66 (0.44 to 1.22) mg/mmol (P<0.001), and carotid-femoral pulse wave velocity from 11.5+/-2.3 to 11.1+/-1.9 m/s (P<0.01). Subgroup analysis showed that the reductions in blood pressure and urinary albumin/creatinine ratio were significant in all groups, and the decrease in pulse wave velocity was significant in blacks only. These results demonstrate that a modest reduction in salt intake, approximately the amount of the current public health recommendations, causes significant falls in blood pressure in all 3 ethnic groups. Furthermore, it reduces urinary albumin and improves large artery compliance. Although both could be attributable to the falls in blood pressure, they may carry additional benefits on reducing cardiovascular disease above that obtained from the blood pressure falls alone. The objectives of the study were to assess the effects of moderate sodium restriction on blood pressure in insulin-dependent diabetic (IDDM) patients with nephropathy and high normal or mildly hypertensive blood pressure (primary objective), and to document possible associated changes of exchangeable body sodium, body volumes, components of the renin-angiotensin-aldosterone system, atrial natriuretic peptide, and catecholamines (secondary objective). Sixteen patients with untreated systolic blood pressure > or = 140 < 160 mmHg and/or diastolic blood pressure > or = 85 < 100 mmHg were included in a double-blind, randomized, placebo-controlled trial. After a 4-week run-in period on their usual diet and a 2-week dietary training period to reduce sodium intake to about 90 mmol/day, eight patients received 100 mmol/day sodium supplement (group 2) and eight patients a matching placebo (group 1) for 4 weeks while continuing on the reduced-sodium diet. Patients were examined at weekly intervals. Main response variables were mean values of supine and sitting systolic and diastolic blood pressure as measured in the clinic and by the patients at home. The differences in blood pressure between the beginning and the end of the blinded 4-week study period were calculated and the differences in changes between the two patient groups were regarded as the main outcome parameters. During the blinded 4-week study period, average urinary sodium excretion was 92 +/- 33 (mean +/- SD) mmol/day in group 1 and 199 +/- 52 mmol/day in group 2 (p = 0.0002). The differences in blood pressure changes between the two patient groups were 3.9(-1.2 to 9) mmHg [mean (95% confidence intervals)] for systolic home blood pressure, 0.9(-3.7 to 5.5) mmHg for diastolic home blood pressure, 4.9(-3.3 to 13.1) mmHg for clinic systolic blood pressure and 5.3(1 to 9.7 mmHg, p = 0.02) for clinic diastolic blood pressure. Combining all patients, there were relevant associations between changes of urinary sodium excretion and blood volume (Spearman correlation coefficient r = 0.57), blood pressure and angiotensin II (diastolic: r = -0.7; systolic: r = -0.48), and exchangeable body sodium and renin activity (r = -0.5). In conclusion, in this study of IDDM patients with nephropathy and high normal or mildly hypertensive blood pressure, a difference in sodium intake of about 100 mmol/day for a period of 4 weeks led to a slight reduction of clinic diastolic blood pressure. Studies including larger numbers of patients with various stages of nephropathy and hypertension are needed to definitely clarify the effects of sodium restriction in IDDM. To determine the effect of moderate dietary sodium restriction on the hypertension of non-insulin-dependent (type II) diabetes.
                Randomised parallel controlled study of moderate sodium restriction for three months compared with usual diabetic diet, followed by randomised double blind crossover trial of sustained release preparation of sodium for one month versus placebo for one month in patients continuing with sodium restriction.
                Patients attending diabetic outpatient clinic of city hospital.
                Thirty four patients with established type II diabetes complicated by mild hypertension (systolic blood pressure greater than 160 mm Hg or diastolic pressure greater than 95 mm Hg on three consecutive occasions). Patients already taking antihypertensive agents (but not diuretics) not barred from study provided that criteria for mild hypertension still met. Conditions precluding patients from study were diabetic or hypertensive nephropathy, cardiac failure, and pregnancy.
                After run in phase with recordings at seven weeks, three weeks, and time zero patients were allocated at random to receive moderate dietary sodium restriction for three months (n = 17) or to continue with usual diabetic diet. Subsequently nine patients in sodium restriction group continued with regimen for a further two months, during which they completed a randomised double blind crossover trial of sustained release preparation of sodium (Slow Sodium 80 mmol daily) for one month versus matching placebo for one month.
                Reduction in blood pressure in type II diabetics with mild hypertension.
                Supine and erect blood pressure, body weight, and 24 hour urinary sodium and potassium excretion measured monthly during parallel group and double blind crossover studies. After parallel group study sodium restriction group showed significant reduction in systolic blood pressure (supine 19.2 mm Hg, erect 21.4 mm Hg; p less than 0.001) and mean daily urinary sodium excretion (mean reduction 60 mmol/24 h). There were no appreciable changes in weight, diabetic control, or diastolic pressure. No significant changes occurred in controls. In double blind crossover study mean supine systolic blood pressure rose significantly (p less than 0.005) during sodium supplementation (to 171 mm Hg) compared with value after three months of sodium restriction alone (159.9 mm Hg) and after one month of placebo (161.8 mm Hg).
                Moderate dietary restriction of sodium has a definite hypotensive effect, which may be useful in mild hypertension of type II diabetes. To determine whether moderate restriction of dietary sodium content or supplementation of potassium intake reduces blood-pressure in patients with mild essential hypertension, twelve patients were put on three different diets--a control diet (180 mmol sodium/day), a sodium restricted diet (80 mmol/day). Each diet was taken for at least 4 weeks and the sequence of the regimens was randomised. At the completion of each regimen intra-arterial pressure was recorded continuously, and vasoactive hormones were measured hourly, for 24 h, under standardised conditions, in hospital. Compared with the control diet, sodium restriction was associated with lower blood-pressure readings in seven patients, higher levels in five, and an overall reduction in mean pressures of only 4.0/3.0 mm Hg (not significant). Individual differences in blood-pressure between these two diets correlated closely with concomitant differences in plasma renin activity (r = 0.75). Potassium supplementation also resulted in variable changes in arterial pressure, and the mean difference in pressure recordings (0.1/0.8 mm Hg) was insignificant. The results show that moderate restriction of sodium intake or supplementation of dietary potassium has variable effects on arterial pressure in individuals with mild essential hypertension, and that overall the blood-pressure changes induced are very small. Responsiveness of the renin-angiotensin system may limit the fall in blood-pressure induced by sodium restriction. A total of 841 healthy men and women aged 25 to 49 years, with diastolic blood pressures of 78 to 89 mm Hg, were randomly assigned to a control treatment group (no dietary counseling) or to one of four dietary counseling treatment groups (reduced calories, reduced sodium, reduced sodium and calories, or reduced sodium and increased potassium). Participants were followed for a 3-year period to assess the effect of dietary changes on blood pressure. After 6 months, counseling had resulted in a net (of control) mean overnight urinary sodium reduction of 13%, a potassium increase of 8%, and a decrease in mean body weight of 7%. At 3 years, the sodium and weight reductions were 10% and 4%, respectively; the potassium change was nil. All four dietary counseling treatment groups had lower mean blood pressures than the control group. The largest net reduction in blood pressure occurred in the calorie group: diastolic pressure was 2.8 mm Hg and 1.8 mm Hg and systolic pressure, 5.1 mm Hg and 2.4 mm Hg at 6 months and 3 years, respectively. All four dietary counseling treatment groups experienced fewer hypertensive events; significantly fewer occurred in the sodium groups. The beneficial effects on blood pressure achieved in this trial have implications for the prevention of cardiovascular disease through dietary reduction of calories and sodium. The present study evaluated the role of nitric oxide (NO) in the systemic vascular and renal adaptation to changes in dietary sodium intake.
                Seven healthy normotensive male subjects were randomized to high or low sodium diets in a double blind crossover design (7 days on each diet). The NO synthesis inhibitor, NGmonomethyl-L-arginine (L-NMMA) was infused systemically (1.8 mg/kg over 30 min) at the end of each dietary period and its effects on blood pressure, renal plasma flow, glomerular filtration rate, urinary flow rate and sodium excretion were measured.
                Blood pressure increased in response to L-NMMA on a high sodium diet only (area under time curve percentage change in mean blood pressure, low sodium = -94.5 +/- 164.3; high sodium = 391.1 +/- 228.6; P < 0.05 low versus high). The increase in blood pressure was directly and significantly associated with the individual salt sensitivity, defined by the difference in systemic mean blood pressure between high and low sodium diets (r = 0.756; P < 0.05). L-NMMA also reduced renal plasma flow and urinary flow rate in subjects on high sodium diet.
                The data support a significant influence of endogenous NO in the systemic and renal vascular adaptation to a high sodium diet in normotensive men. In addition, the direct association between the individual sodium-sensitivity and the pressor response to L-NMMA suggests that there is increased dependence of vascular tone on NO in normotensive subjects whose blood pressure is more sodium sensitive. We investigated the effect of a 4-day oral salt load (150 mmol NaCl extra per day) on blood pressure, erythrocyte sodium transport and the activity in the renin-angiotensin system in six males with primary hypertension, who had attained normotension on chronic enalapril treatment for 4 years. The design was a placebo-controlled, randomized, two-way cross over, double-blind study, i.e. each patient served as his own control. Intracellular erythrocyte sodium and potassium content were measured by flame photomometry. The increase in the intracellular sodium concentration during 1 h in 37 degrees C incubation of whole-blood with ouabain (compared with no-ouabain) was measured to determine the rate of active sodium efflux. 24-h blood pressure registration was performed with Space-lab equipment (SL 90202) before and at the end of the salt load. Left ventricular morphology was evaluated with echocardiography and the minimal vascular resistance of the hand vascular bed with water plethysmography at baseline and after 4 years on enalapril. Four years' enalapril treatment caused a significant decrease in blood pressure, left ventricular mass and minimal vascular resistance. During the 4-day salt load average 24-h blood pressure was significantly elevated, 129+/-3/85+/-2 mmHg as compared to 124+/-2/82+/-2 mmHg during placebo treatment (p=0.025). The change (delta) in MAP during high salt intake showed a negative relationship to delta-sodium efflux rate constant (r=-0.65, p=0.047). No significant relationship was found between the blood pressure response to the salt load and structural cardiovascular changes. In conclusion, a short-term oral salt load in hypertensive patients on chronic enalapril treatment caused a blood pressure rise, which was related to cellular sodium transport but not to structural cardiovascular changes. Plasma renin activity was measured at baseline and 6 months in a trial of nonpharmacologic therapy of mild hypertension to determine whether plasma renin activity predicts the diastolic blood pressure (DBP) response to nonpharmacologic therapy.
                Randomized controlled trial of volunteers from the general community with mild hypertension (DBP between 90 and 100 mm Hg), off all antihypertensive therapy at baseline, treated in special research clinics (n = 593).
                Subjects were randomly assigned to usual, weight loss, or low sodium/high potassium diet and then randomly assigned to receive placebo, chlorthalidone, or atenolol.
                Renin was analyzed as plasma renin activity and as a renin index (logarithm of 24-hour urinary sodium excretion times logarithm of plasma renin activity) (593 patients at baseline and 6 months) to correct for varied sodium intakes. The DBP was measured using the random zero device.
                Change in DBP at 6 months could be predicted from baseline plasma renin activity or renin index. The DBP was decreased after 6 months of therapy by 2 mm Hg for each unit increase in baseline plasma renin activity and by 0.16 mm Hg for each unit increase in baseline renin index. Patients in the highest renin index quartile had a greater DBP response to atenolol therapy, and patients in the lowest renin index quartile had a greater DBP response to chlorthalidone therapy. Weight loss diet achieved a greater reduction in DBP in patients with higher baseline renin index and had an additive effect on DBP response in both of the drug groups. Patients on a weight loss diet receiving placebo in the highest baseline renin index quartile had a reduction in DBP of 12.4 mm Hg, compared with 4.4 mm Hg in the lowest baseline renin index quartile (P = .009). A low sodium/high potassium diet had a lesser effect than a weight loss diet on pharmacologic therapy. As with the weight loss diet, patients on a low sodium/high potassium diet in the highest baseline renin index quartile had a greater reduction in DBP than patients in the lowest baseline renin index quartile.
                These data suggest a significant relationship between baseline levels of plasma renin index and the likelihood of success of nonpharmacologic treatment of hypertension. The possibility exists that dietary modification may increase the number of patients who remain normotensive after drug withdrawal. In an effort to resolve this question, former Hypertension Detection and Follow-up Program Stepped Care participants (n = 496) were randomized into four major groups at the end of the programme (greater than 5 years antihypertensive therapy): controls (continue medication); discontinue medication, no dietary intervention; discontinue medication and weight loss; discontinue medication and reduce sodium. Groups 1, 2 and 4 were further divided into obese (greater than or equal to 120% ideal weight, and non-obese groups). The weight reduction group (greater than or equal to 120% ideal weight) lost 10.1 +/- 11 lbs without changing dietary sodium (n = 87). The sodium restriction group reduced urine sodium excretion from 145 to 97 mEq per day (n = 169). Sixty per cent of the weight loss group were normotensive at 56 weeks compared to 35% withdrawn from medication without dietary intervention. The highest 56 weeks success rates were in the mild non-overweight hypertensives on sodium restriction (78%), and the mild overweight hypertensives on weight reduction (72%). Randomization to either weight loss group or sodium restriction group increased the likelihood of remaining off drugs (adjusted odds ratio of 3.43 for the weight group and 2.17 for the sodium group (P less than 0.05). Age, severe hypertension greater than 5 years previous to entry into Dietary Intervention Study of Hypertension (DISH) or need for several drugs increased the chance of failure. 1. Responses of adrenomedullin to acute and chronic salt loading were examined in normotensive and hypertensive subjects. 2. In the acute salt load study, isotonic saline (50 ml/kg for 1 h) was intravenously infused into nine normotensive subjects and 11 patients with essential hypertension. Plasma adrenomedullin was higher in hypertensive than in normotensive subjects but was unchanged by saline infusion in either the normotensive (before infusion, 2.4 +/- 0.2 fmol/ml; after infusion, 2.4 +/- 0.1 fmol/ml) or hypertensive (before infusion, 3.0 +/- 0.1 fmol/ml; after infusion, 2.9 +/- 0.2 fmol/ml) group, while renin was suppressed and atrial natriuretic peptide was markedly increased. Plasma endothelin was not affected either. 3. In the chronic salt load study, seven normotensive subjects and 23 patients with essential hypertension underwent two 7-day periods of 30 and 260 mmol/day sodium intake. Depending on the blood pressure change, 13 hypertensive subjects were classified as salt-resistant and 10 as salt-sensitive. Salt-sensitive hypertensive subjects had suppressed plasma renin activity even during low salt intake. Plasma adrenomedullin or endothelin were not affected by the salt intake changes in any group; however, the high salt intake increased atrial natriuretic peptide in all groups. 4. These data indicate that the circulating level of adrenomedullin is not changed by either acute or chronic salt loading in normotensive subjects and patients with essential hypertension. Animal studies have indicated that increased nitric oxide (NO) synthesis plays a significant role in the renal adaptation to increased sodium intake. To investigate the role of NO during increased sodium intake in humans, we studied the effect of acute, systemic injection of NG-monomethyl-L-arginine (L-NMMA) on renal hemodynamics [glomerular filtration rate and renal plasma flow (GFR and RPF, respectively)], urinary sodium excretion (FENa), systemic hemodynamics [mean arterial blood pressure and heart rate (MAP and HR)], and plasma levels of several vasoactive hormones in 12 healthy subjects during high (250 mmol/day) and low (77 mmol/day) sodium intake in a crossover design. The sodium diets were administered for 5 days before the L-NMMA treatments, in randomized order, with a washout period of 9 days between each diet and L-NMMA treatment. GFR and RPF were measured using the renal clearance of 51Cr-labeled EDTA and 125I-labeled hippuran by the constant infusion technique in clearance periods of 30-min duration. Two baseline periods were obtained, after which L-NMMA was given (3 mg/kg over 10 min), and the effect of treatment was followed over the next five clearance periods. During high sodium intake, L-NMMA induced a more pronounced relative decrease in RPF (P = 0.0417, ANOVA), a more pronounced relative decrease in FENa (P = 0.0032, ANOVA), and a more pronounced relative increase in MAP (P = 0.0231, ANOVA). During low sodium intake, the effect of L-NMMA on FENa was abolished. During low sodium intake, L-NMMA induced a sustained drop in plasma renin (31 +/- 5 vs. 25 +/- 5 microU/ml, P < 0.001), which was not seen during high sodium intake. The data indicate that increased production of NO is an important part of the adaptation to increased dietary sodium intake in healthy humans, with respect to renal hemodynamics, sodium excretion, and the secretion of renin. Some observations suggest that a strict low-salt diet may induce unfavourable metabolic side-effects. The main aim of this study was to analyse the possible consequences of severe salt restriction in mildly hypertensive patients.
                The study was carried out through a randomized double-blind protocol.
                Forty-seven ambulatory patients proceeding from the hypertension unit were initially admitted: 17 were lost, and 30 non-diabetic mildly hypertensives (DBP 90-104 mmHg) with normal renal function completed the protocol.
                After a wash-out period, patients were maintained on a low-salt intake (2.8 +/- 1.0 g day-1 of NaCl) and placebo for 2 weeks, and the same diet and salt supplements (11.7 +/- 2.5 g day-1 of NaCl) for another 2 weeks, separated by a second wash-out period.
                At the end of each dietary period, blood pressure (BP) and body weight were measured, and a blood sample was taken for determination of routine serum chemistries, plasma lipid and apolipoprotein concentrations, immunoreactive insulin (IRI), and plasma renin activity (PRA). Urinary 24 h excretion of sodium and potassium were measured.
                During the salt restriction period BP did not change, weight lowered, and PRA raised. There was a significant increase in serum level of creatinine, uric acid, IRI, total cholesterol and apo B, and a decrease in HDL cholesterol and apo A-I.
                As previously suggested, these observations seem to indicate that strict salt restriction may cause, at least in the short-term, adverse metabolic changes in hypertensive patients. To test the short-term feasibility and efficacy of seven nonpharmacologic interventions in persons with high normal diastolic blood pressure.
                Randomized control multicenter trials.
                Volunteers recruited from the community, treated and followed up at special clinics.
                Of 16,821 screenees, 2182 men and women, aged 30 through 54 years, with diastolic blood pressure from 80 through 89 mm Hg were selected. Of these, 50 did not return for follow-up blood pressure measurements.
                Three life-style change groups (weight reduction, sodium reduction, and stress management) were each compared with unmasked nonintervention controls over 18 months. Four nutritional supplement groups (calcium, magnesium, potassium, and fish oil) were each compared singly, in double-blind fashion, with placebo controls over 6 months.
                Primary: change in diastolic blood pressure from baseline to final follow-up, measured by blinded observers. Secondary: changes in systolic blood pressure and intervention compliance measures.
                Weight reduction intervention produced weight loss of 3.9 kg (P less than .01), diastolic blood pressure change of -2.3 mm Hg (P less than .01), and systolic blood pressure change of -2.9 mm Hg (P less than .01). Sodium reduction interventions lowered urinary sodium excretion by 44 mmol/24 h (P less than .01), diastolic blood pressure by 0.9 mm Hg (P less than .05), and systolic blood pressure by 1.7 mm Hg (P less than .01). Despite good compliance, neither stress management nor nutritional supplements reduced diastolic blood pressure or systolic blood pressure significantly (P greater than .05).
                Weight reduction is the most effective of the strategies tested for reducing blood pressure in normotensive persons. Sodium reduction is also effective. The long-term effects of weight reduction and sodium reduction, alone and in combination, require further evaluation. To provide a firmer basis for preventing high blood pressure (BP), we tested interventions to promote weight loss, dietary sodium reduction, and their combination for lowering diastolic BP, systolic BP, and the incidence of hypertension during a 3- to 4-year period.
                We conducted a randomized, 2 x 2 factorial, clinical trial, with BP levels measured by blinded observers. Nine academic medical centers recruited 2382 men and women (age range, 30-54 years) not taking antihypertensive drugs, with a diastolic BP of 83 to 89 mm Hg, a systolic BP lower than 140 mm Hg, and a body mass index (the weight in kilograms divided by the square of the height in meters) representing 110% to 165% of desirable body weight. Counseling aimed at helping participants achieve their desirable weight or a 4.5-kg or more weight reduction (in the weight loss and combined groups) and/or sodium intake of 80 mmol/d (in the sodium reduction and combined groups) was provided.
                From baseline, participants' weight decreased by 4.3 to 4.5 kg at 6 months and by approximately 2 kg at 36 months in the weight loss and combined groups compared with weight changes in the usual care group (all groups, P < .001). Sodium excretion decreased 50 and 40 mmol/d at 6 and 36 months, respectively, in the sodium reduction group and about 15 mmol/d less at each time point in the combined group compared with the usual care group (all groups, P < .01). Compared with the usual care group, BP decreased 3.7/2.7 mm Hg in the weight loss group, 2.9/1.6 mm Hg in the sodium reduction group, and 4.0/2.8 mm Hg in the combined group at 6 months (all groups, P < .001). At 36 months, BP decreases remained greater in the active intervention groups than in the usual care group (weight loss group, 1.3/0.9 mm Hg; sodium reduction group, 1.2/0.7 mm Hg; combined group, 1.1/0.6 mm Hg). Differences were statistically significant for systolic and diastolic BP in the weight loss group and for systolic BP in the sodium reduction group. Through 48 months, the incidence of hypertension (BP > or = 140 mm Hg systolic or > or = 90 mm Hg diastolic or the use of antihypertensive drugs) was significantly less in each active intervention group than the usual care group (average relative risks, 0.78-0.82).
                In overweight adults with high-normal BP, weight loss and reduction in sodium intake, individually and in combination, were effective in lowering systolic and diastolic BP, especially in the short-term (6 months). Although the effects on average BP declined over time, reductions in hypertension incidence were achieved. Nonpharmacologic interventions are frequently recommended for treatment of hypertension in the elderly, but there is a paucity of evidence from randomized controlled trials in support of this recommendation.
                To determine whether weight loss or reduced sodium intake is effective in the treatment of older persons with hypertension.
                Randomized controlled trial.
                A total of 975 [corrected] men and women aged 60 to 80 years with systolic blood pressure lower than 145 mm Hg and diastolic blood pressure lower than 85 mm Hg while receiving treatment with a single antihypertensive medication.
                Four academic health centers.
                The 585 obese participants were randomized to reduced sodium intake, weight loss, both, or usual care, and the 390 nonobese participants were randomized to reduced sodium intake or usual care. Withdrawal of antihypertensive medication was attempted after 3 months of intervention.
                Diagnosis of high blood pressure at 1 or more follow-up visits, or treatment with antihypertensive medication, or a cardiovascular event during follow-up (range, 15-36 months; median, 29 months).
                The combined outcome measure was less frequent among those assigned vs not assigned to reduced sodium intake (relative hazard ratio, 0.69; 95% confidence interval [CI], 0.59-0.81; P<.001) and, in obese participants, among those assigned vs not assigned to weight loss (relative hazard ratio, 0.70; 95% CI, 0.57-0.87; P<.001). Relative to usual care, hazard ratios among the obese participants were 0.60 (95% CI, 0.45-0.80; P<.001) for reduced sodium intake alone, 0.64 (95% CI, 0.49-0.85; P=.002) for weight loss alone, and 0.47 (95% CI, 0.35-0.64; P<.001) for reduced sodium intake and weight loss combined. The frequency of cardiovascular events during follow-up was similar in each of the 6 treatment groups.
                Reduced sodium intake and weight loss constitute a feasible, effective, and safe nonpharmacologic therapy of hypertension in older persons. Hypertension is a major modifiable risk factor, and while sodium restriction in hypertensive patients appears effective, its role in normotensive individuals remains unclear. We assessed the effect of a low vs. high-sodium diet on blood pressure in normotensive Indo-Asian adults.
                A randomized, controlled, crossover trial was conducted on 200 normotensive subjects randomly selected from the general population in Karachi, Pakistan. Participants were randomized to either a low (20 mEq/day) or a high-sodium diet (220 mEq/day) for 1 week, followed by 1 week of washout, then the alternate diet for 1 week. The primary outcome was difference in systolic blood pressure (SBP) measured at the end of each phase in the overall population.
                Mean (95% confidence interval) decline in 24-h urinary sodium excretion was 81.0 (69.6-92.4) mEq/day (P < 0.001), and in SBP was 1 (0-3)mm Hg (P = 0.17) between high and low-sodium phase. A significant interaction was detected (P = 0.001) between dietary sodium and baseline SBP with a greater adjusted mean (95% confidence interval) decline in SBP (6 (2-9)mm Hg) among participants with high-normal SBP (130-139 mm Hg) and no significant change (-1(-2 to 1)) in those with normal baseline SBP (<130 mm Hg), respectively.
                Reducing sodium intake has a beneficial effect on blood pressure in Indo-Asians with high-normal SBP, at least in the short term. Given the ubiquity of high-normal blood pressure (BP), and frank hypertension in this population, we argue that primary prevention strategies, targeted at use of discretionary sodium, should now be designed and evaluated. Parental history of hypertension, dietary sodium, and psychological stress have all been implicated in the development of essential hypertension and may interact in elevating disease risk. The mechanism by which this might occur is unclear, but it may be related to changes in the peripheral vasculature. The present study examined the effects of parental history and sodium on cardiovascular responses to an extended stressor. Eighteen normotensive offspring of hypertensives and 18 offspring of normotensives were exposed to a 1-hour shock-avoidance video-game procedure after 14 days of sodium loading (10 1-g tablets/day) and again after 14 days of placebo tablets. Order of sessions was counterbalanced between subjects in a double-blind design. In offspring of hypertensives, sodium loading elevated total peripheral resistance and norepinephrine responses to stress relative to placebo conditions and compared with offspring of normotensives. These increases were accompanied by decreases in stroke volume and cardiac output, which may explain the absence of familial differences in blood pressure responses to stress and sodium. Sodium loading had no effect on offspring of normotensives. The elevated resistance in offspring of hypertensives may suggest the initiation of pathological processes. The absence of sodium effects on resting values indicates the importance of research under conditions of stress. Improved cardiovascular survival during statin treatment might be due to effects in addition to cholesterol lowering. We hypothesize that sodium intake affects renal function and vasoactive hormones in atorvastatin-treated healthy subjects.
                In a randomized, placebo-controlled, double-blind, crossover study we measured the effect of a moderate change in sodium intake on glomerular filtration rate (GFR), blood pressure (BP), renal tubular function, plasma concentrations of vasoactive hormones and urinary excretion of aquaporin-2 (u-AQP2) in 22 healthy subjects. The subjects were randomized to standardized fluid intake and diet corresponding to the need for calories in the 4 days before each of the 2 examination days. In one of the periods they were randomized to receive sodium chloride tablets (2 g) thrice daily for 4 days. Two doses of atorvastatin (80 mg) were given; one at 2200 h the evening before the study day, the other at 0830 h in the morning.
                24-h urinary sodium excretion increased by 23%. GFR and BP were unchanged. Sodium clearance, fractional excretion of sodium and u-AQP2 increased, whereas free water clearance decreased during high sodium intake. PRC and aldosterone were suppressed during the high sodium diet.
                A change in dietary sodium intake of approximately 100 mmol daily does not change GFR and BP in atorvastatin-treated healthy men. The lack of change in BP might reflect that the subjects studied were not sodium sensitive, or that atorvastatin treatment modified sodium sensitivity. We examined the reproducibility of dietary salt-sensitivity testing by studying the effects on blood pressure (BP) of low sodium intake (20 mmol/day) and high sodium intake (220 mmol/day) in 10 men with borderline hypertension on two separate occasions. A difference in mean arterial pressure of 8 mm Hg between the high salt and the low salt regimen was arbitrarily chosen to define salt sensitivity. In addition, the reproducibility of changes in renal haemodynamics and in humoral factors, such as plasma renin activity, plasma aldosterone, atrial natriuretic peptide and urinary dopa and dopamine excretion, on the alteration in sodium intake were studied. As far as changes in BP are concerned, there was perfect agreement between the two tests, because in the second investigation, all subjects were classified in the same category as before. The salt-induced changes in plasma atrial natriuretic peptide and in renal excretion of dopa (dihydroxyphenylalanine) and dopamine were repeatedly and consistently different between the salt-sensitive and the salt-resistant group. The study revealed no support for a role of renal haemodynamics or the renin-angiotensin-aldosterone system in the pathophysiology of salt-induced elevations of BP in salt-sensitive subjects. To evaluate the metabolic effects of modification of sodium intake in patients with essential hypertension.
                Thirteen patients with essential hypertension (10 M, median age 51 yrs, range 21-64) followed in random order a low-sodium and a high-sodium diet (50 mmol Na/day vs 250 mmol/day for two weeks each). At the end of each diet an evaluation was made of 24 hour blood pressure (ABPM, Spacelabs 90207) and serum concentration of: glucose, total and HDL cholesterol, uric acid, lipoproteins A, B, Lp(a), total proteins, albumin.
                Twenty-four hours systolic and diastolic BP were significantly higher at the end of high sodium diet than of low sodium diet [respectively 132 mmHg (120-161) vs 128 mmHg (109-150); p = 0.008 and 84 mmHg (71-99) vs 81 mmHg (70-95); p = 0.008)]. No significant variations were found as regards serum glucose and lipidic parameters between low and high sodium diets. Serum uric acid was significantly higher following low sodium diet [5.9 mg/dl (4.5-8) vs 4.6 mg/dl (3.4-6.5); p = 0.003)], as well as serum total proteins [7.2 g/dl (6.9-8.2) vs 7 g/dl (6.5-7.8); p = 0.027)]. A significant direct correlation was found between changes of uric acid and total proteins from low to high sodium diet (Spearman's rho = 0.57; p = 0.04).
                In patients with essential hypertension a moderate dietary sodium restriction, able to reduce significantly 24 hours arterial pressure, does not worsen serum glucose nor lipids concentration. Patients with untreated heart failure (HF) exhibit a blunted hemodynamic and neuroendocrine response to a high sodium intake, leading to excessive sodium and water retention. However, it is not known whether this is the case for patients with compensated HF receiving angiotensin-converting enzyme inhibitors and beta-adrenoreceptor blockers. Therefore, we determined the hemodynamic and neuroendocrine responses to 1 wk of a low-sodium diet (70 mmol/day) and 1 wk of a high-sodium diet (250 mmol/day) in 12 HF patients and 12 age-matched controls in a randomized, balanced fashion. During steady-state conditions, hemodynamic and neuroendocrine examinations were performed at rest and during bicycle exercise. In seated HF patients, high sodium intake increased body weight (1.6 +/- 0.4%), plasma volume (9 +/- 2%), cardiac index (14 +/- 6%), and stroke volume index (21 +/- 5%), whereas mean arterial pressure was unchanged. Therefore, the total peripheral resistance decreased by 10 +/- 4%. Similar hemodynamic changes were observed during an incremental bicycle exercise test. Plasma concentrations of angiotensin II and norepinephrine were suppressed, whereas plasma pro-B-type natriuretic peptide remained unchanged. In conclusion, high sodium intake was tolerated without any excessive sodium and water retention in medically treated patients with compensated HF. The observation that high sodium intake improves cardiac performance, induces peripheral vasodilatation, and suppresses the release of vasoconstrictor hormones does not support the advice for HF patients to restrict dietary sodium. 28 patients who had a sustained diastolic blood pressure of 95 to 104 mm Hg and who had no treatment for it for at least 13 months before the trial, but who were otherwise unselected, took part in a randomised controlled trial in which the effect of a restricted sodium diet was compared with that of a general health package. The general health package did not include any specific hypotensive procedures. Changes in blood pressure were measured at predetermined intervals over the course of a year. Within each group both systolic and diastolic blood pressure fell to a highly significant extent after a year, but there was no significant difference between the groups. It would thus seem that the antihypertensive effect of a restricted sodium diet may be related to the increased consultation and monitoring activity of such intervention rather than to the dietary manipulation itself. In order to examine the effect of dietary sodium intake on plasma lipids, 15 healthy male volunteers were given a low-salt diet (20 mmol/day) for 3 weeks, adding either placebo, sodium chloride (200 mmol/day), or a non-chloride sodium salt (sodium citrate, 200 mmol Na/day) for one week each, in a single-blind randomized crossover study. Plasma levels of total cholesterol and LDL cholesterol were significantly higher at the end of the placebo period than with either sodium chloride (by 8.7 and 11.9%, respectively) (P less than 0.005) or sodium citrate (by 11.3% and 16.8%, respectively) (P less than 0.005). Thus this effect was dependent on sodium but not on chloride intake. Triglyceride and HDL-cholesterol levels were not affected by the dietary regimens. We conclude that short-term dietary sodium restriction may lead to a rise in plasma total and LDL cholesterol, thereby possibly increasing the risk of atherosclerotic vascular disease. Our findings render it possible that diuretic-induced lipid disturbances may also be caused by sodium depletion. Few trials have evaluated the effects of reduced sodium intake in older individuals, and no trial has examined the effects in relevant subgroups such as African Americans.
                The effects of sodium reduction on blood pressure (BP) and hypertension control were evaluated in 681 patients with hypertension, aged 60 to 80 years, randomly assigned to a reduced sodium intervention or control group. Participants (47% women, 23% African Americans) had systolic BP less than 145 mm Hg and diastolic BP less than 85 mm Hg while taking 1 antihypertensive medication. Three months after the start of intervention, medication was withdrawn. The primary end point was occurrence of an average systolic BP of 150 mm Hg or more, an average diastolic BP of 90 mm Hg or more, the resumption of medication, or a cardiovascular event during follow-up (mean, 27.8 months).
                Compared with control, mean urinary sodium excretion was 40 mmol/d less in the reduced sodium intervention group (P<.001); significant reductions in sodium excretion occurred in subgroups defined by sex, race, age, and obesity. Prior to medication withdrawal, mean reductions in systolic and diastolic BPs from the reduced sodium intervention, net of control, were 4.3 mm Hg (P<.001) and 2.0 mm Hg (P =.001). During follow-up, an end point occurred in 59% of reduced sodium and 73% of control group participants (relative hazard ratio = 0.68, P<.001). In African Americans, the corresponding relative hazard ratio was 0.56 (P =.005); results were similar in other subgroups. In dose-response analyses, end points were progressively less frequent with greater sodium reduction (P for trend =.002).
                A reduced sodium intake is a broadly effective, nonpharmacologic therapy that can lower BP and control hypertension in older individuals. Stroke is directly related to blood pressure and treatment trials in older hypertensive individuals show a reduction in strokes. However, the majority of strokes occur in normotensive individuals in whom no attempt is made to lower blood pressure. We compared the effects of modest salt restriction on blood pressure in older hypertensive and normotensive people.
                47 untreated elderly people (24 men, age range 60-78 years; blood-pressure range 123-205 mm Hg systolic and 64-112 mm Hg diastolic) completed a 2-month double-blind randomised placebo-controlled crossover study of modest salt restriction with slow sodium and placebo to give a salt intake of either 10 g (equivalent to the normal amount for the UK population) or 5 g.
                On the normal salt intake for the UK population, supine blood pressure was 163/90 (SD 21/10) mm Hg with urinary sodium excretion of 177 (49) mmol/day. With modest sodium restriction, blood pressure fell to 156/87 (22/9) mm Hg (p < 0.001/0.004) with a urinary sodium excretion of 94 (50) mmol/day. A reduction in sodium intake of 83 mmol/day was associated with a reduction of 7.2/3.2 mm Hg. There was no significant difference in the blood-pressure fall between 18 normotensive and 29 hypertensive participants (8.2/3.9 vs 6.6/2.7 mm Hg).
                A modest reduction in salt intake leads to a fall in blood pressure in both normotensive and hypertensive older people similar to that in outcome trials of thiazide-based treatment. Since the majority of strokes in older people occur below the current definition of hypertension, our results have important implications for the prevention of stroke. Sodium restriction can reduce blood pressure in hypertensive patients. The present study indicates that if hypertension is well controlled then the reemergence of hypertension can be decreased by the use of a reduced sodium intake. The present paper demonstrates that in such patients on a normal salt diet, 90% become hypertensive within 6 months while only 40% of people on a reduced sodium diet become hypertensive. It is proposed that a high sodium intake activates a number of amplifiers that causes a shift of the dose-response curve to sodium to the left and if not prevented or interrupted leads to the development of hypertension. Dietary sodium reduction and, as necessary, pharmacologic treatment are recommended for hypertension management. This prospective, randomized, open-label, blinded-end point, multicenter, crossover study investigated the effect of dietary sodium intake on mean ambulatory systolic blood pressure (maSBP) in patients with hypertension receiving aliskiren 300 mg once daily. Following a 2- to 4-week washout period, patients were randomized to a high- (≥ 200 mmol/d) or low- (≤ 100 mmol/d) sodium diet and were started on aliskiren, 300 mg/d. After 4 weeks, patients were crossed over to the alternate diet for an additional 4 weeks. The primary efficacy variable was change in maSBP between diets. During treatment with aliskiren, maSBP was significantly lower with the low-sodium diet compared with the high-sodium diet (least squares mean difference, 9.4 mm Hg; 95% CI, 7.5-11.4; P < .0001). The percentage of patients achieving a maSBP response to aliskiren (<130 mm Hg or a ≥ 20-mm Hg reduction from baseline) was greater with the low- (76.5%) versus the high-sodium diet (42.6%; P < .0001). Overall, 40.9% patients had ≥ 1 adverse event and the rates were similar between groups. In this study, aliskiren was well tolerated and a low-sodium diet accentuated its antihypertensive effect. A controlled prospective study compared two groups of obese hypertensive subjects during 12 weeks of a hypocaloric protein-supplemented fast containing 40 mEq of sodium daily. One group received additional sodium chloride sufficient to maintain baseline sodium intake measured prior to the fast (210 m/Eq/day). Sodium restriction resulted in greater weight loss and slightly greater BP reduction only during the initial week of fasting. Thereafter, despite sodium equilibrium, further substantial weight loss and BP reduction were identical in both groups, the decrement in weight being linear (1.89 kg/wk) and the BP reduction asymptotic. Although the initial reduction in BP during the first week of supplemented fast may be attributable to negative salt and water balance, the further reduction in BP during a period of constant sodium balance must be caused by weight loss per se or by the triggering of other antihypertensive mechanisms associated with weight reduction. 1. Salt restriction is recommended in the treatment of hypertension and is included in national dietary guidelines, but its effect on exercise in hot conditions has not been extensively studied. 2. The effects of 2 weeks on two levels of salt intake (50 and 150 mmol/day) on the ability to exercise (60% of maximal oxygen uptake) in a hot environment (35 degrees C) were studied in eight healthy normotensive subjects. 3. All subjects were able to complete the exercise load on the two levels of salt intake. No differences in mean oxygen uptake, heart rate or rectal temperature during exercise were observed between the two salt intakes. 4. Plasma sodium, potassium and osmolality were similar on the two salt intakes both before and during exercise. Plasma renin activity and aldosterone concentration were elevated after 2 weeks on the reduced salt intake and remained so during exercise. 5. The estimated sweat rate during exercise was similar on the two salt intakes but the loss of sodium was less on the low salt intake. 6. On the basis of these results it is concluded that moderate salt restriction does not impair the ability to exercise in a hot environment. Forty young subjects, aged 18 to 28 years, with mildly elevated blood pressure participated in a double-blind randomized three-period crossover study of the effect of sodium restriction with and without potassium supplementation on blood pressure. Dietary sodium intake was restricted for 18 weeks in which the patients received in random sequence 'slow-sodium' (90 mmol/day), 'slow-potassium' (72 mmol/day), and placebo tablets, each for 6 weeks. Mean urinary sodium excretion was 129 mmol/24 h in the slow-sodium period, 57 mmol/24 h during placebo, and 69 mmol/24 h during slow-potassium. Mean supine systolic blood pressure in the sixth week of the slow-potassium period was 3.3 mmHg lower than that at the end of the slow-sodium period (P less than 0.05). There was no significant difference in systolic or diastolic blood pressure between the placebo and the slow-sodium periods. The fall in systolic blood pressure in the low sodium/high potassium period was accompanied by a fall in cardiac index of 0.4 l/min per m2 body surface area (BSA) (P = 0.03). Our observations suggest a small hypotensive effect of moderate sodium restriction combined with high potassium intake in young hypertensive subjects. Sodium restriction alone has little effect on blood pressure in this group. The combination of a low sodium/high potassium diet may lower blood pressure by affecting cardiac output. Reducing the dietary sodium:potassium ratio may therefore be useful in the management of early primary hypertension. There is still a need of support for nonpharmacologic treatment of uncomplicated, mild-to-moderate essential hypertension. We investigated whether a low sodium-based diet implemented by a nutritionist could lower blood pressure and affect sympathetic activity. Middle-aged, otherwise healthy men with never-treated essential hypertension (n = 95) were randomized to an intervention group, a blood pressure control group, and a time control group. The intervention group was advised to use less sodium chloride in their diet, and if necessary, less saturated fat and decrease body weight. They attended regular clinic visits as did the blood pressure control group. After 1 year, the intervention group had achieved on average 72 mmol/24 h lower urinary sodium excretion (P < .001) and a decrease in body weight of 2.7 +/- 0.5 kg (P < .001). Both supine and standing mean blood pressure were on average 8 to 10 mm Hg lower after intervention compared with the two control groups (P < .001). Arterial plasma epinephrine, measured in all 40-year-old subjects (n = 30), decreased in parallel in all three groups (P < .05), indicating some habituation to the invasive procedure and clinic visits. However, the decrease in norepinephrine was significant (P < .001) only in the intervention group; it correlated with the weight loss (r = 0.76, P < .05) and was significantly higher (P < .05) than in both control groups. These results suggest that broad dietary advice (ie, low intake of sodium chloride, saturated fat and energy), implemented by a nutritionist, may have a significant blood pressure lowering effect and a favorable sympathicolytic effect in uncomplicated, mild-to-moderate essential hypertension. When the function of the renin system is inhibited, blood pressure becomes more dependent on changes in sodium and water balance. Diuretics alone and sodium restriction alone are additive to converting enzyme inhibitor therapy. However, it is not known if these two ways of reducing sodium balance are additive in the presence of established converting enzyme inhibition. We therefore performed a double-blind crossover study of the effects of moderate sodium restriction in 21 patients with essential hypertension who were already being treated with the combination of a converting enzyme inhibitor and a diuretic. After 1 month of captopril (50 mg twice daily) and hydrochlorothiazide (25 mg once daily) therapy, with their usual sodium intake, average supine blood pressure was 147/96 +/- 5/3 (SEM) mm Hg 2 hours after treatment. Patients then reduced their sodium intake to around 80-100 mmol/day for the remainder of the study. After 2 weeks of sodium restriction, they entered a double-blind, randomized, crossover study of Slow Sodium (100 mmol sodium/day) compared with Slow Sodium placebo, while continuing sodium restriction and the above treatment. During the double-blind study, after 1 month of treatment with captopril (50 mg twice daily), hydrochlorothiazide (25 mg once daily), and Slow Sodium placebo, supine blood pressure 2 hours after treatment was 138/88 +/- 4/2 mm Hg (24-hour urinary sodium 104 +/- 11 mmol). After 1 month of captopril (50 mg twice daily), hydrochlorothiazide (25 mg once daily), and Slow Sodium tablets, supine blood pressure 2 hours after treatment was 147/91 +/- 5/2 mm Hg (p less than 0.05; 24-hour urinary sodium 195 +/- 14 mmol).(ABSTRACT TRUNCATED AT 250 WORDS) Cross-sectional studies on human hypertension have suggested an association between sodium intake and left ventricular hypertrophy (LVH).
                The effects on LVH of a nonpharmacological treatment program based mainly on sodium restriction were examined by serial echocardiography in a 12-month controlled, randomized study that included 76 previously untreated subjects with uncomplicated mild-to-moderate hypertension. The mean daily sodium excretion of 38 subjects randomized into the treatment group decreased from 195 +/- 95 to 94 +/- 73 mmol (P < .001) at 6 months and to 109 +/- 74 mmol (P < .001) at 12 months. This was accompanied by a weight decrease from 81.4 +/- 18.0 to 79.2 +/- 17.4 kg (P < .001) at 6 months and to 80.6 +/- 17.5 kg (NS) at 12 months. The net blood pressure decrease (difference in change from baseline between the treatment and control groups) was 8.9 mm Hg (P < .001) in systolic blood pressure and 6.5 mm Hg (P < .001) in diastolic blood pressure during the first 6 months and 6.7 mm Hg (P < .01) in systolic blood pressure and 3.8 mm Hg (P < .01) in diastolic blood pressure during the last 6 months. After 12 months of sodium restriction, left ventricular mass (LVM) had decreased by 5.4% (from 238 +/- 63 to 225 +/- 51 g, P < .01), and LVM index (LVMI) had decreased by 4.7% (from 123 +/- 26 to 117 +/- 22 g/m2, P < .05), whereas no changes occurred in these parameters in the control group. In treated subjects with baseline LVMI of more than the median value of 133 g/m2 in men and 107 g/m2 in women, LVM decreased by 8.6% (from 272 +/- 62 to 249 +/- 51 g, P < .01), and LVMI decreased by 7.1% (from 140 +/- 23 to 130 +/- 22 g/m2, P < .01). LVM and LVMI remained unchanged in treated subjects with LVMI values equal to or less than the median.
                Our data suggest that long-term nonpharmacological treatment with moderate sodium restriction decreases LVH. Eighty-five subjects, aged 31-55 years, suffering from uncomplicated essential hypertension and receiving no regular medication were randomized to sodium restriction and control groups. Systolic (SBP) and diastolic (DBP) blood pressure were measured during an orthostatic test at baseline and after 6 months sodium restriction. The mean daily sodium excretion of 43 treated subjects decreased from 193 +/- 91 mmol to 95 +/- 70 mmol (p less than 0.001). Treated patients were divided on the basis of their mean overall out-patient clinic (OC) DBP decrease in the sitting position during the 6 months (monthly measurements) into sodium-sensitive (DBP decrease greater than 10 mmHg, n = 17), indeterminate (DBP decrease 5-10 mmHg, n = 18) and sodium-resistant (DBP decrease less than 5 mmHg, n = 8) subgroups. At 6 months the level of DBP in the supine position was lower than at baseline in both sensitive and resistant subgroups, whereas in the standing position a lower DBP than at baseline was seen only in the sodium-sensitive subgroup. The magnitude of the subsequent OC DBP decrease was significantly associated with a high baseline seated OC DBP (p less than 0.001) and a high, for baseline OC DBP adjusted orthostatic DBP increase (p = 0.014). Our data suggest that posture should be included in the concept of sodium sensitivity and that an orthostatic test is useful in the prediction of seated and standing DBP decrease produced by moderate, long-term sodium restriction. The purpose of the present study was to examine the effects of salt-restriction alone and in combination with an angiotensin-converting enzyme (ACE) inhibitor (cilazapril) on both office and ambulatory blood pressure (BP) levels in free living subjects with elevated BP. The study was carried out in an out-patient setting with subjects recruited from occupational health care system mainly. After exclusions, 39 subjects (24 men, 15 women, aged 28-65 years) with mildly to moderately elevated BP completed the study. After 3 months run-in period with placebo (first month on normal-salt and the next 2 months on sodium-restricted diet) the subjects were randomised into either salt-restriction placebo or salt-restriction cilazapril (2.5 mg daily) groups for 3 months. In the whole group, 24-h urinary sodium excretion decreased (mean +/- s.d.) from 198 +/- 60 to 112 +/- 59 mmol (4 weeks vs 24 weeks, P < 0.001). Systolic and diastolic office BP decreased during the placebo-sodium-restriction phase (-7.1 [95% Cl -11.2; -3.0] and -4.2 [95% Cl -6.6; -1.8] mm Hg for systolic and diastolic BP), and similarly the daytime ambulatory BP (ABP) was reduced during this period (-2.8 [95% Cl -5.2; -0.5] and -2.8 [95% Cl -4.5; -1.2] mm Hg, systolic (SBP) and diastolic blood pressure (DBP) respectively). No changes were observed in the night time ABP. Addition of cilazapril to sodium-restriction enhanced significantly the office BP (-13.2, [95% Cl -20.2; -6.2], and -9.1 [95% Cl -13.5; -4.7]) and daytime ABP (-5.9, [95% Cl -10.1; -1.8] and -5.3, [95% Cl -8.8; -1.9]) reduction. Blood glucose, plasma insulin or serum lipids did not change during the study. Moderate sodium restriction seems to lower the office and daytime ABP levels in subjects with mild-to-moderate hypertension. The antihypertensive effect of cilazapril could be enhanced by sodium restriction. To examine the interactions between sodium balance and the sympathetic nervous system, we studied eight normotensive men after high (800 mEq/day) and low (10 mEq/day) sodium intake. We measured blood pressure (BP), arterial, venous, and urinary norepinephrine (NE) before and during incremental infusion of NE. We found significant direct, linear relationships (p less than 0.001) between the dose of NE infused and arterial and venous NE levels, and with mean arterial BP at both levels of sodium balance. In addition. the sensitivity was greater and the threshold of pressor response to NE as well as the basal concentrations of NE in arterial and venous plasma significantly lower (p less than 0.05) after the high sodium period. These observations expose heretofore unrecognized qualitative and quantitative interactions between sodium balance and NE that are capable of influencing BP in man. In 25 outpatients with essential hypertension, sodium sensitivity, defined as the difference in mean arterial pressure (delta MAP) between 2 weeks of high-sodium (300 mmol per day) and 2 weeks of low-sodium (LS) intake (50-100 mmol per day), was studied in relation to the plasma norepinephrine (NE) level, NE release, and pressor response to intravenous NE. In addition, forearm blood flow (FBF) was measured by plethysmography. There were two control periods of regular sodium intake, one of 4 weeks' duration at the beginning of the study and one of 2 weeks' duration at the end. The delta MAP ranged from +18 to -8 mm Hg. The eight patients in whom delta MAP was greater than 10 mm Hg were regarded as salt-sensitive. When compared with salt-insensitive subjects, salt-sensitive patients had higher plasma NE levels in the control period (p less than 0.05) and after 2 weeks of HS intake (p less than 0.01). Sodium sensitivity was directly related to the change in plasma NE between the HS and LS periods (p less than 0.001). The NE release decreased in salt-insensitive subjects whereas it increased in salt-sensitive patients between the LS and HS periods. Changes in NE release were directly related to sodium sensitivity (p less than 0.05). The pressor response to NE was not significantly influenced by changes in sodium intake. The FBF fell in salt-sensitive patients and increased in salt-insensitive subjects between the LS and HS periods. Sodium sensitivity was directly related to the change in forearm vascular resistance (p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS) We studied the effect of high and low NaCl diets in normotensive and borderline hypertensive subjects to determine if a high NaCl diet produces abnormal renal vasoconstriction during the stress of upright posture in borderline hypertensive subjects. We studied 13 normotensive young men with diastolic blood pressures below 85 mm Hg and nine borderline hypertensive young men defined by diastolic blood pressures intermittently above 90 mm Hg. The subjects achieved comparable sodium balance during 6 days of low NaCl (10 mEq Na, 40 mEq Cl, 100 mEq K) and high NaCl (400 mEq Na, 400 mEq Cl, 100 mEq K) diets. In the normotensive subjects, standing for 30 minutes resulted in a tendency for diastolic blood pressure to fall during both diets. In contrast, during standing borderline hypertensive subjects showed no change in diastolic blood pressure during the low salt diet and a tendency for diastolic blood pressure to increase after the high salt diet. Standing reduced renal plasma flow in both groups during both diets. However, only during the high NaCl diet did the absolute decrease and percent decrease in renal plasma flow during standing differ significantly (p less than 0.05 and p less than 0.01, respectively) between the borderline hypertensive (-151 +/- 24 ml/min/1.73m2; -29 +/- 4%) and normotensive subjects (-79 +/- 17 ml/min/1.73m2; -15 +/- 3%). The resultant increase in the renal vascular resistance index with standing did not differ between the two groups during the low NaCl diet.(ABSTRACT TRUNCATED AT 250 WORDS) An ouabain-like factor has been implicated repeatedly in salt-sensitive hypertension as a natriuretic agent. However, the response of plasma ouabain-like factor to acute and chronic variation of body sodium is unclear. We studied 138 patients with essential hypertension who underwent an acute volume expansion/contraction maneuver (2 days) and 20 patients who entered a blind randomized crossover design involving chronically controlled sodium intake and depletion (170 to 70 mmol/d; 2 weeks each period). In both studies, plasma levels of ouabain-like factor were higher during sodium depletion (acute: 338.8+/-17.4 and 402.7+/-22.8 pmol/L for baseline and low sodium, respectively, P<0.01; chronic: 320.4+/-32.0 versus 481.0+/-48.1 pmol/L, P=0.01). No significant change in plasma ouabain-like factor was observed after a 2-hour saline infusion (333.4+/-23.9 pmol/L) or controlled sodium (402.1+/-34.9 pmol/L). When patients were divided into salt-sensitive or salt-resistant groups, no differences in plasma ouabain-like factor were observed in the 2 groups at baseline or in response to the 2 protocols: salt resistant (n=69, 340.1+/-25.9 pmol/L) versus salt sensitive (n=69, 337.4+/-23.6 pmol/L) and chronic salt resistant (n=11, 336.0+/-53.2) versus salt sensitive (n=9, 301.1+/-331.4 pmol/L). However, circulating ouabain-like factor was increased by sodium depletion in both groups. These results demonstrate that circulating ouabain-like factor is raised specifically by maneuvers that promote the loss of body sodium. Acute expansion of body fluids with isotonic saline is not a stimulus to plasma ouabain-like factor. Moreover, basal levels of plasma ouabain-like factor do not differ among patients with salt-sensitive or salt-resistant hypertension. Taken together, these new results suggest that ouabain-like factor is involved in the adaptation of humans to sodium depletion and argue against the hypothesis that ouabain-like factor is a natriuretic hormone. To examine the effect of a reduced sodium and increased potassium and magnesium intake on blood pressure.
                Randomised double blind placebo controlled trial.
                General population of a suburb of Rotterdam.
                100 men and women between 55 and 75 years of age with untreated mild to moderate hypertension.
                During 24 weeks the intervention group received a mineral salt (sodium: potassium: magnesium 8:6:1) and foods prepared with the mineral salt. Controls received common salt and foods.
                Change in blood pressure.
                Complete follow up was achieved for 97 of the 100 randomised subjects. Systolic blood pressure (mean of measurements at weeks 8, 16, and 24) fell by 7.6 mm Hg (95% confidence interval 4.0 to 11.2) and diastolic blood pressure by 3.3 mm Hg (0.8 to 5.8) in the mineral salt group compared with the controls, with a 28% decrease in urinary sodium excretion and a 22% increase in urinary potassium excretion. Twenty five weeks after the study the difference in blood pressure between the groups was no longer detectable.
                Replacing common sodium salt by a low sodium, high potassium, high magnesium mineral salt could offer a valuable non-pharmacological approach to lowering blood pressure in older people with mild to moderate hypertension. This study determined the relative efficacy of aerobic exercise (daily walking) and moderate dietary sodium restriction (sodium intake <100 mmol/day) for reducing systolic blood pressure (SBP) and pulse pressure (PP) in postmenopausal women with elevated initial levels, and the potential role of reductions in large artery stiffness in these changes.
                Lifestyle behaviors are recommended for lowering blood pressure (BP) in adults with elevated baseline levels, but there is little information as to the relative efficacy of different interventions or the mechanisms underlying their potential beneficial effects.
                After baseline measurements and random assignment, 35 nonmedicated healthy postmenopausal women with SBP between 130 and 159 mm Hg completed three months of either aerobic (walking) exercise (n = 18; 62 +/- 9 years, mean +/- SD) or moderate dietary sodium restriction (SR) (n = 17; 65 +/- 10 years, mean +/- SD).
                Body mass and composition, plasma volume, and fasting concentrations of metabolic coronary risk factors did not differ between the groups at baseline or change with intervention. Systolic BP and PP at rest decreased with both exercise and SR (p < 0.05); however, the reductions were three- to fourfold greater with SR (p < 0.05). Sodium restriction, but not exercise, also reduced 24-h SBP and PP (p < 0.05). Aortic pulse wave velocity (PWV) and carotid augmentation index were reduced only with SR (p < 0.05). Changes in SBP and PP at rest and over 24 h correlated with the corresponding changes in aortic PWV (r = 0.53 to 0.61, p < 0.01).
                Moderate SR lowers SBP and PP in postmenopausal women with elevated baseline levels more than does daily walking. The greater blood pressure reductions with SR may be mediated in part by a decrease in the stiffness of the large elastic arteries. The efficacy of once-a-day cilazapril (a new long acting converting enzyme inhibitor) therapy for the 24 h control of hypertension and its effects on the renin-angiotensin axis were investigated. Twenty-four uncomplicated hypertensive patients whose sitting diastolic blood pressures remained within 94 to 114 mmHg after four weeks of placebo were randomly assigned on a double-blind basis to receive either continued placebo or cilazapril therapy at a single dose of 1.25, 2.5 or 5.0 mg/day for a further four weeks. At the end of weeks 4 and 8, systolic and diastolic blood pressures and heart rates were recorded, supine and standing, at 0, 2, 4, 6, 9, 12 and 24 h following a single dose of drug. At the same times, blood was withdrawn for determination of plasma renin activity and aldosterone. Supine and erect systolic and diastolic blood pressures were lowered to normotensive levels with an optimal response being achieved at a dose of 2.5 mg/day. Supine and erect heart rates were unchanged with respect to drug dosage, and the reflex increase in heart rate and diastolic blood pressure on changing from supine to erect posture was maintained in all groups. Maximum antihypertensive efficacy was from 2 to 6 h after drug ingestion. There were no changes in resting aldosterone, but plasma renin activity was increased at all drug dosages. A single 2.5 mg dose of cilazapril provides blood pressure control for a 24 h period. Cilazapril does not appear to interfere with the reflex autonomic responses to postural change. Moderate salt restriction is of debatable efficacy in the treatment of mild or moderate hypertension; however, salt restriction enhances the activity of most antihypertensive drugs. Some observations suggest that the antihypertensive activity of calcium antagonists is not increased or could even decrease with dietary salt restriction. In the present work 15 patients suffering arterial hypertension and normal renal function are studied during four two week periods; a) unrestricted diet and medication, b) unrestricted diet and nifedipine (40 mg/day), c) low salt diet (5 g of salt/day) and nifedipine, and d) the same low salt diet, nifedipine and a salt supplement (6 g/day); salt or placebo were given in a double blind manner. At the end of each period arterial blood pressure was recorded, a urine sample for sodium determination was taken, and a blood sample was drawn for serum renine activity and biochemical parameters; at the end of each period patients' weight was recorded. Blood pressure significantly decreased (systolic: 9.83%, and dyastolic 11.17%) in patients treated with nifedipine, with no differences observed with salt modifications. Urinary sodium reflected correctly dietary salt modifications. Serum renine activity significantly increased during salt restriction. No significant changes were observed in weight or in the biochemical parameters studied. These results seem to suggest that the antihypertensive effect of nifedipine in patents suffering mild to moderate essential hypertension, with no change observed is not altered by the amount of salt in diet, at least within the limits studied (89.7 to 190 mEq/day of Sodium). Combined hormonal oral contraceptives (OCs) may lead to a mild rise in blood pressure and body weight. In rare instances, large increments in blood pressure are measured. We investigated the effect of a combination of ethinyl estradiol (EE) plus a progestogen with antimineralocorticoid, i.e. natriuretic, properties [Drospirenone (DRSP)] on body weight, blood pressure, the renin-aldosterone system, atrial natriuretic factor, plasma lipids, and glucose tolerance. It is anticipated that this will lead to the development of an OC that does not raise body weight or blood pressure. Four groups of 20 women each received 30 micrograms EE plus 3 mg DRSP (group A), 20 micrograms EE plus 3 mg DRSP (group B), 15 micrograms EE plus 3 mg DRSP (group C), and, as a control OC, 30 micrograms EE plus 150 micrograms levonorgestrel (Microgynon, Schering; group D) for 6 months. During the OC-free control cycles before and after treatment and throughout treatment, the target parameters were measured. Between the pretreatment cycle and the sixth treatment cycle, mean body weight fell by 0.8 to 1.7 kg in groups A, B, and C (P < 0.05 vs. D), whereas it rose by 0.7 kg in group D. Systolic and diastolic blood pressures fell by 1-4 mm Hg in groups A, B, and C (significant for A and C vs. D) and increased by 1-2 mm Hg in group D. Renin substrate rose equally in all groups (P < 0.05), whereas PRA and plasma aldosterone rose significantly only in the DRSP groups, presumably due to sodium loss. In the DRSP groups, high density lipoprotein cholesterol rose (P < 0.05), in contrast to group D. Low density lipoprotein cholesterol fell slightly (P > 0.05), whereas triglyceride levels showed a stronger increase in the DRSP groups (P < 0.05) than in group D. All groups attained good cycle control; group A had the best. Side-effects were minimal. To our knowledge, this is the first report on a combined OC that leads to a small decrease in body weight and blood pressure. It may be especially beneficial for women susceptible for a gain in weight and a rise in blood pressure. The angiotensin II (AT II) type I receptor antagonist losartan has been reported to increase urinary uric acid and potassium excretion. These effects might be beneficial in cyclosporin (CsA)-treated renal transplant recipients, who frequently suffer from hyperuricaemia and hyperkalaemia.
                In this prospective, open, randomized, two-way cross-over study we included 13 hypertensive CsA-treated patients after renal transplantation and administered either the angiotensin-converting enzyme (ACE) inhibitors enalapril or losartan. Laboratory parameters, 24-h urinary protein excretion, and mean 24-h arterial blood pressure (MAP) were checked after 3 weeks treatment with enalapril, after a wash-out period of 2 weeks, and before and after a 3-week treatment course with losartan.
                Both drugs slightly reduced MAP (losartan from 97+/-6 to 94+/-9 and enalapril to 93+/-8 mmHg). Serum potassium levels significantly increased during enalapril therapy (from 4.3+/-0.5 to 4.8+/-0.4 mmol/l, P<0.05), as did, although not significantly, uric acid concentrations (from 7.8+/-1.9 to 8.2+/-1.8 mg/dl, P=0.5). Losartan, on the contrary, only mildly affected serum potassium (4.3+/-0.5 vs 4.5+/-0.5 mmol/l, P=0.25) and serum uric acid decreased (from 7.8+/-2.4 to 7.3+/-1.8 mg/dl, P=0.6). Serum aldosterone and urinary aldosterone excretion were significantly reduced only during ACE inhibitor treatment, which might explain the variable effects on potassium homeostasis.
                Losartan may be a useful agent to reduce blood pressure and serum uric acid levels in renal transplant recipients treated with CSA: Furthermore, in this high-risk population, the effects on serum potassium levels are less marked with losartan than with enalapril. Insulin-dependent diabetes mellitus (IDDM) patients may have an increased intrarenal angiotensin II activity. In diabetic patients, captopril increases the renal hemodynamic response to an amino acid infusion. We investigated the effects of two salt diets on arterial pressure and renal response to a protein load in 10 normotensive (blood pressure < 140/90 mm Hg) IDDM patients (aged 30 +/- 3 years) who had diabetes for 7 +/- 4 years and normoalbuminuria levels [albumin excretion rate 4.8 (2.5-19.1) microg/min]. After 1 week of normal (approximately 100 mmol/day; approximately 100 mEq/l) and 1 week of high (approximately 300 mmol/day; approximately 300 mEq/l) salt intake, renal hemodynamic studies were performed at baseline and after a protein load (meat meal) of 100 g/1.73 m2. The mean 24-hour urinary sodium excretion levels were 99 +/- 27 and 293 +/- 80 mmol (mEq) with normal and high salt intake, respectively. No significant changes were seen in plasma sodium and glucose control with the normal and high salt diets, respectively: plasma sodium 135 +/- 3 vs. 137 +/- 1 mmol/l (mEq/l), (p = 0.08) and glycated hemoglobin 9.1 +/- 1.9 vs. 9.4 +/- 2.1% (p = 0.36). The body weight (70.9 +/- 12 vs. 71.8 +/- 13 kg; p = 0.015) was significantly higher with a high salt diet. The mean arterial pressure was similar with both diets (normal vs. high salt diet 91 +/- 9 vs. 89 +/- 6 mm Hg, p = 0.25). The plasma renin concentration [28 +/- 15 vs. 16 +/- 6 microU/ml(168 +/- 90 vs. 96 +/- 36 pmol/l), p = 0.013] and angiotensin II [8.8 +/- 4.4 vs. 6.4 +/- 3.5 pg/ml (0.052 +/- 0.025 vs. 0.038 +/- 0.021 nmol/l), p = 0.016] were significantly lower with the high salt diet. Following protein loading, the glomerular filtration rate increased with both diets: normal salt diet 114 +/- 26 vs. 128 +/- 30 ml/min/1.73 m2(1.9 +/- 0.43 vs. 2.13 +/- 0.50 ml/s/1.73 m2), p = 0.04; high salt diet 118 +/- 23 vs. 127 +/- 29 ml/min/1.73 m2 (1.97 +/- 0.38 vs. 2.12 +/- 0.48 ml/s/1.73 m2), p = 0.13. The change in renal plasma flow was similar to that of the glomerular filtration rate with normal and high salt intake, respectively: 566 +/- 94 vs. 617 +/- 142 ml/min/1.73 m2 (9.44 +/- 1.57 vs. 10.29 +/- 2.37 ml/s/173 m2), p = 0.0017; 572 +/- 125 vs. 600 +/- 110 ml/min/1.73 m2 (9.54 +/- 2.08 vs. 10.00 +/- 1.83 ml/s/1.73 m2), p = 0.057. In this subset of normotensive normoalbuminuric IDDM patients, a high salt intake did not promote an exaggerated renal response to the protein load despite inhibition of the renin-angiotensin system. Nineteen unselected patients with mild to moderate essential hypertension, whose average supine blood pressure after two months' observation on no treatment was 156/98 mm Hg, were advised not to add salt to food and to avoid sodium-laden foods. After 2 weeks of sodium restriction patients were entered into an 8-week double-blind randomised crossover study of 'Slow Sodium' (Ciba) versus slow sodium placebo. The mean supine blood pressure was 7.1 mm Hg (6.1%) lower in the fourth week of placebo than that in the fourth week of slow sodium (p less than 0.001). Urinary sodium excretion in the fourth week of slow sodium was 162 +/- 9 mmol/24 h and that in the fourth week of placebo was 86 mmol +/- 9 mmol/24 h (p less than 0.001). There was no difference in potassium excretion. These results suggest that moderate sodium restriction achieved by not adding salt and avoiding sodium-laden foods should, if not already, become part of the management of essential hypertension. We evaluated the effect on serum lipids of sodium intake in 2 diets. Participants were randomly assigned to a typical American control diet or the Dietary Approaches to Stop Hypertension (DASH) diet, each prepared with 3 levels of sodium (targeted at 50, 100, and 150 mmol/d per 2100 kcal). The DASH diet is increased in fruits, vegetables, and low-fat dairy products and is reduced in saturated and total fat. Within assigned diet, participants ate each sodium level for 30 days. The order of sodium intake was random. Participants were 390 adults, age 22 years or older, with blood pressure of 120 to 159 mm Hg systolic and 80 to 95 mm Hg diastolic. Serum lipids were measured at baseline and at the end of each sodium period. Within each diet, sodium intake did not significantly affect serum total cholesterol, LDL cholesterol, HDL cholesterol, or triglycerides. On the control diet, the ratio of total cholesterol-to-HDL cholesterol increased by 2% from 4.53 on higher sodium to 4.63 on lower sodium intake (P=0.04). On the DASH diet, sodium intake did not affect this ratio. There was no dose-response of sodium intake on serum lipids or the cholesterol ratio in either diet. At each sodium level, total cholesterol, LDL cholesterol, and HDL cholesterol were lower on the DASH diet versus the typical American diet. There were no significant interactions between the effects of sodium and the DASH diet on serum lipids. In conclusion, changes in dietary sodium intake over the range of 50 to 150 mmol/d did not affect blood lipid concentrations. The effect of dietary salt restriction on blood pressure was measured in patients with moderate hypertension receiving antihypertensive medication. Patients were studied during a randomly allocated 6 week period of moderate dietary salt restriction and during a 6 week period of normal diet. Twenty-four of twenty-eight patients achieved a reduction of salt excretion exceeding 20%. In these patients mean urinary sodium excretion fell from 169 (s.e.m. = 13) mmol/24 h to 92 (s.e.m. = 7) mmol/24 h. Potassium excretion and body weight did not change, and with the exception of the erect systolic pressure, there was no overall change in blood pressure. When the data were grouped according to the patient medication, mean supine systolic pressure fell from 148.9 (s.e.m. = 4.4) to 140.3 (s.e.m. = 5.0) mmHg (n = 14, P greater than 0.05) and mean supine diastolic pressure fell from 100.8 (s.e.m. = 2.9) to 97.0 (s.e.m. = 2.8) mmHg (n = 14, P greater than 0.05) in patients taking diuretics. Blood pressure did not change in patients whose medication did not include diuretics. Moderate dietary salt restriction may be therapeutically useful in patients with moderate hypertension treated with diuretics but is of little value in those not receiving diuretics. To elucidate the sequential mechanisms underlying cyclosporin-induced hypertension and nephrotoxicity.
                A study of healthy males over the first 9 days of drug ingestion to permit the detection of serial changes in renal function and blood pressure in a situation free from the confounding variables of concomitant disease or drugs.
                Double-blind, placebo-controlled, randomized crossover study with cyclosporin (5 mg/kg twice a day) or placebo. Blood pressure and urinary sodium excretion were measured each day, and glomerular filtration rate (GFR) and effective renal plasma flow (ERPF) were measured on days 1, 4, 7 and 9. Cholesterol, lipoprotein (a) and endothelin were measured on days 1 and 9.
                GFR decreased by 9% with cyclosporin and was significantly lower than with placebo on day 4 of therapy. ERPF fell by 24%. The fall in GFR correlated significantly with suppressed plasma renin activity (P < 0.0001). Cyclosporin-induced hypertension occurred in the absence of any change in urinary sodium output or in plasma endothelin. Cyclosporin did not affect lipoprotein (a) levels during 9 days of cyclosporin therapy.
                Cyclosporin-induced hypertension and renal vasoconstriction are well established after 9 days of cyclosporin 5 mg/kg twice a day. We found no evidence to implicate either circulating endothelin or renal sodium retention in the onset of cyclosporin-induced hypertension. Cyclosporin-induced renal vasoconstriction appeared to occur when the protective mechanism of plasma renin activity suppression became exhausted. To evaluate the behavior of active kallikrein excretion in salt-sensitive and salt-resistant hypertensive patients during changes in sodium-chloride (NaCl) intake, 61 male, nonobese, nondiabetic outpatients affected by uncomplicated essential hypertension were given a diet that contained 140 mmol NaCl per day for 2 wk. Patients then received either a low- (20 mmol NaCl/day) or a high- (320 mmol NaCl/day) sodium diet for 2 wk, according to a randomized, double-blind, cross-over protocol. Hypertensive patients were classified as salt sensitive when their diastolic blood pressure rose by at least 10 mm Hg after the high-sodium diet, and decreased by at least 10 mm Hg after the low-sodium diet, considering as baseline blood pressure values those that were taken at the end of the 140 mmol NaCl/day intake period. The remaining patients were classified as salt resistant or, when diastolic blood pressure increased by 10 mm Hg or more after low-sodium intake, as counter-regulating. Twenty-three patients were therefore classified as salt sensitive, 28 as salt resistant, and 10 as counter-regulating. The baseline active kallikrein excretion was significantly lower (P < 0.0001) in salt-sensitive (0.62 +/- 0.31 U/24 h) patients than in salt-resistant (1.39 +/- 0.44 U/24 h) and counter-regulating patients (1.27 +/- 0.38 U/24 h). Surprisingly, the kallikrein response to changes in sodium intake was similar in all subgroups, although enzyme excretion was always at the lowest level in salt-sensitive hypertensive patients. This latter group also showed the highest plasma atrial natriuretic peptide levels (28.2 +/- 8.5 fmol/mL, P < 0.0001 versus salt-resistant and counter-regulating patients), and the greatest peptide increment with sodium load (P < 0.0001 versus salt-resistant and counter-regulating patients). Counter-regulating patients showed the steepest increase in plasma renin activity (from 0.24 +/- 0.18 to 0.83 +/- 0.21 ng/L per s, P < 0.001) and decrease of plasma atrial natriuretic peptide (from 26.1 +/- 6.3 to 6.8 +/- 3.1 fmol/mL, P < 0.001) when switched from a high to a low-sodium intake. In conclusion, salt-sensitive hypertensive patients excrete less active kallikrein than do salt-resistant and counter-regulating patients, but maintain a normal enzyme response to changes in dietary sodium intake. The exaggerated response of atrial natriuretic peptide to high-sodium intake that was observed in the same patients could be compensating for an impaired renal capability to excrete a sodium load. We assessed blood pressure (BP), body weight, renal hemodynamics, and insulin sensitivity (by euglycemic-hyperinsulinemic clamp) in nine normoalbuminuric and seven microalbuminuric IDDM patients after 6 days on a low-sodium diet (20 mEq) and after 6 days on a high-sodium diet (250 mEq). In microalbuminuric but not in normoalbuminuric IDDM patients, switching from a low to a high-sodium diet was associated with a significant increase in mean BP (from 92 +/- 3 to 101 +/- 4 mmHg; P < 0.001) and in body weight (2.91 +/- 0.63 vs. 1.47 +/- 0.26 kg; P < 0.05). Moreover, under high-sodium conditions, angiotensin II infusion (3 ng x kg(-1) x min(-1)) caused a greater increase in mean BP (14 +/- 2 vs. 7.4 +/- 1 mmHg; P < 0.05) and a smaller reduction in renal plasma flow (-122 +/- 29 vs. -274 +/- 41 ml x min(-1) x 1.73 m2; P < 0.05) in microalbuminuric than in normoalbuminuric IDDM patients. Under low sodium conditions, aldosterone increments after angiotensin II infusion were lower (P < 0.05) in microalbuminuric than in normoalbuminuric IDDM patients. Insulin-mediated glucose disposal was not affected by sodium dietary content, but it was lower in microalbuminuric (P < 0.05) than in normoalbuminuric IDDM patients. The salt-induced changes in mean BP were related to insulin sensitivity (r = -0.78; P < 0.001). In conclusion, in IDDM patients, microalbuminuria is associated with 1) an increased responsiveness of BP to salt intake and angiotensin II, 2) impaired modulation of renal blood flow, and 3) insulin resistance. Therefore, salt sensitivity in IDDM patients clusters with other factors that are likely to play an important role in the pathogenesis of diabetic nephropathy and its cardiovascular complications. The aims of the present study were to investigate the effects of changes in sodium intake in patients with untreated mild essential hypertension on the hormonal (plasma renin activity and aldosterone) and renal tubular responses to short-term hyperinsulinemia as achieved by an oral glucose tolerance test (OGTT). Fourteen patients with essential hypertension (mean age, 46 years; average blood pressure (BP), 151/96 mm Hg) were studied. After a 1 week run-in period on their usual diet they entered a randomized double-blind crossover study of a week of low (10 mmol/day) vs a week of high (350 mmol/day) sodium intake. On the last day of each diet they underwent a standard 2-h OGTT. Blood and urines were taken hourly and segmental tubular sodium handling was assessed by the endogenous lithium clearance. The results demonstrate that the plasma insulin and glucose response to a short-term oral glucose load were not influenced significantly by the changes in dietary sodium intake. However, the glucose load was associated with marked renal sodium retention in the absence of any change in systemic BP. The reduction in renal sodium excretion was independent of circulating aldosterone but appeared to be due to an increase in renal distal tubular re-absorption. To explore the effect of short-term cholesterol-lowering treatment with atorvastatin on erythrocyte sodium-lithium countertransport (Na(+)/Li(+) CT) activity.
                Group A consisted of 30 patients (14 men) with mild essential hypertension (systolic blood pressure (SBP), 140-159 mm Hg and/or diastolic BP, 90-99 mm Hg) and primary hypercholesterolemia low-density lipoprotein (LDL) cholesterol >4.1 mmol/l and triglycerides (TG) <2.8 mmol/l), group B of 30 normotensive patients (16 men) with primary hypercholesterolemia, while 37 (18 men) healthy volunteers comprised the control group. After a 6-week dietary lead-in, all eligible patients were prescribed 20 mg/day of atorvastatin. Anthropometric data, blood-pressure (BP) measurements and determinations of lipid, non-lipid metabolic parameters (including homeostasis model assessment index, (HOMA-IR)) and erythrocyte Na(+)/Li(+) CT activity were collected at baseline and after 12 weeks of treatment.
                At baseline Na(+)/Li(+) CT activity was significantly higher in group A and B compared with the control group and correlated directly with obesity indices, systolic and diastolic BP, total cholesterol, LDL-cholesterol, TG, apolipoprotein B (apoB), HOMA-IR, uric acid and inversely with high-density lipoprotein (HDL)-cholesterol and apoA1. Systolic and diastolic BP levels, HOMA-IR and Na(+)/Li(+) CT activity were significantly decreased after atorvastatin treatment in both patient groups. The reduction in Na(+)/Li(+) CT activity correlated with baseline Na(+)/Li(+) CT activity and the changes in HOMA-IR values.
                Short-term treatment with atorvastatin for patients with hypercholesterolemia, and with or without essential hypertension, is associated with a significant reduction in the erythrocyte Na(+)/Li(+) CT activity, BP levels and insulin resistance independent of concomitant changes in lipid parameters. High blood pressure and proteinuria are the major risk factors for cardiovascular and renal disease. In black individuals, there is an increased risk of hypertension, stroke, heart failure, and kidney disease. There are no controlled studies of the effects of reducing salt intake on blood pressure and urine protein excretion in black individuals. Therefore, the aim of our study was to determine the effects of modest salt restriction on blood pressure and urine protein excretion in nondiabetic black hypertensive subjects. The study was randomized, double blind, and placebo controlled. After run-in periods on their usual diet and on reduced salt, participants continued to restrict their salt intake and then received either slow sodium tablets, designed to bring their salt intake back to normal, or placebo tablets for 4 weeks in a randomized, double-blind, crossover study. In the 40 who completed the study, urinary sodium excretion fell on slow sodium to placebo from 169+/-73 to 89+/-52 mmol per 24 hours (P<0.001; approximately 10 to 5 g salt per day). Blood pressure fell from 159/101+/-13/8 to 151/98+/-13/8 mm Hg (P<0.01). Protein excretion fell from 93+/-48 mg to 75+/-30 mg per 24 hours (P<0.008). Thus, reducing salt intake from approximately 10 to 5 g per day reduced blood pressure and urine protein excretion in black hypertensives. In light of these findings, we would recommend that all black individuals with raised blood pressure reduce their salt intake to < or =5 g per day. A 15 week randomised double blind placebo controlled trial of oral potassium supplements (48 mmol daily) was conducted in 37 patients who had mildly increased blood pressure and a normal dietary intake of sodium. After a two month run in and a one week baseline period the patients were randomly assigned to receive either potassium supplements (n = 18) or placebo (n = 19). By the third week of treatment blood pressure in the actively treated group had decreased significantly compared with that in the placebo group, though the decrease reached its maximum after 15 weeks. Urinary potassium excretion increased significantly in the group who received potassium supplements, but no significant changes were found in plasma sodium and potassium concentrations or in urinary sodium excretion. In a subgroup of 13 patients who underwent a further nine weeks of treatment with oral potassium supplements at half of the previous dose (24 mmol daily) their blood pressure, at the end of this second study period, was still significantly lower compared with their baseline value but not with that of the placebo group. These results show that moderate oral potassium supplements are associated with a long term reduction in blood pressure in patients who have mild hypertension. To evaluate salt sensitivity in elderly subjects with different forms of hypertension and controls and to investigate any modulation by genotype
                Randomized, double-blinded, placebo-controlled latin-square
                Tertiary referral hospital
                Community subjects (n = 46) aged > or = 60 years classified as isolated systolic hypertension [ISH; systolic blood pressure (SBP) > or = 160, diastolic blood pressure (DBP) < 90 mmHg, n = 19], diastolic +/- systolic hypertension (SDH; DBP > or = 90 mmHg, n = 10) and normotension (SBP < 160, DBP < 90 mmHg, n = 17).
                Four 14 day treatments, 50, 100, 200 and 300 mmol/day of sodium chloride supplementation interspersed with 14 day washout periods on a salt-restricted diet.
                The 24 h blood pressure, heart rate, weight, urinary sodium and creatinine clearance measured during baseline, treatment and washout periods and angiotensinogen (AGT) and angiotensin converting enzyme (ACE) genotypes.
                For the entire cohort, the mean +/- standard error (SE) of change from baseline in SBP for 50, 100, 200 and 300 mmol/day salt was 7.7+/-2.4, 12.1+/-2.4, 16.6+/-3.0, 18.5+/-2.6 mmHg, respectively. For DBP, the respective changes were: -0.1+/-1.5, 2.4+/-1.6, 3.0+/-1.5, 5.8+/-1.7 mmHg. The increase in SBP among ISH subjects was significantly higher than among subjects in the SDH and normotensive groups (P < 0.05). AGT genotype influenced the effect of salt dose on the change in DBP (P = 0.006) but not SBP (P = 0.7).
                In healthy, older subjects, a linear increase in BP occurred with increasing salt dose, it appeared most pronounced in ISH subjects and could be modulated by AGT genotype. In chronic heart failure, a diuretic plus an angiotensin-converting enzyme (ACE) inhibitor only partially suppresses aldosterone despite the fact that aldosterone has many harmful effects independent of angiotensin II. These possible harmful effects of aldosterone are magnesium loss, increased cardiac sympathetic activity, and increased ventricular arrhythmias. We have therefore assessed whether adding the aldosterone antagonist, spironolactone, to a loop diuretic and ACE inhibitor reverses any of these potentially harmful effects of residual aldosterone. In a preliminary animal study, we found that exogenous aldosterone reduced myocardial norepinephrine uptake by 24% in anesthetized rats in vivo. In our main study, 42 patients with New York Heart Association II to III congestive heart failure were randomized to spironolactone (50 to 100 mg/day, titrated to blood pressure and plasma potassium) or placebo in a double-blind fashion. Our principal finding is that cardiac norepinephrine uptake as assessed by 123I-metaiodobenzylguanidine scintigraphy increased with spironolactone (p < 0.01). Spironolactone also elevated plasma magnesium (p < 0.05), reduced urinary magnesium excretion (p < 0.05), and caused a reduction in ventricular arrhythmias on 24-hour ambulatory electrocardiography (p < 0.05). Spironolactone increased plasma renin activity, plasma aldosterone (p < 0.01), 24-hour urinary sodium excretion (p < 0.05), and urinary sodium/potassium ratio (p < 0.01). Echocardiographic-determined measurements of left ventricular systolic and diastolic function were unaltered by spironolactone.(ABSTRACT TRUNCATED AT 250 WORDS) The object of the study was to evaluate blood pressure, insulin and glucose metabolism, and serum lipids in hypertensive patients, during 8 weeks on a moderately salt-restricted diet. A double-blind, cross-over study was conducted with hypertensive patients following a moderately salt-restricted diet. Patients were randomised to sodium capsules in one period and placebo capsules during the other period. After a 1-month run-in period, 13 males and three females with mild to moderate essential hypertension (mean age 50 years) complied with a salt-reduced diet. They were randomized to a salt-supplemented group (5 capsules of 10 mmol sodium per capsule) or a salt reduced diet group (5 capsules of placebo) with cross-over after 8 weeks. Serum insulin, insulin C-peptide, and glucose were measured, fasting and 30 min after a 75-g glucose load. Serum lipids and lipoproteins constituting an atherogenic index were measured, along with blood pressure and 24-h urine excretion of sodium and chloride. Non-significant reductions of systolic and diastolic blood pressure (4 mmHg, p = 0.06, and 2 mmHg, p = 0.13, respectively) were observed during the reduced-salt period. The changes observed for fasting insulin, insulin C-peptide, glucose, serum lipids and the atherogenic index were also non-significant. It is concluded that moderate salt restriction seems not to adversely influence insulin resistance or serum lipids in hypertensive patients. 1. Previous studies of endogenous atrial natriuretic peptide (ANP) in humans have examined changes in plasma levels, rather than regional secretion and clearance of the peptide. Using arterial and selective venous catheterization and sampling, and measurement of regional organ flow, we measured haemodynamics, cardiac secretion of ANP and renal clearance of ANP in six healthy volunteers at rest, on a normal sodium diet. 2. Salt restriction decreases plasma concentrations of ANP. We assessed the contribution of the heart and kidney to this decrease, by measuring cardiac secretion and renal clearance of ANP at the termination of a low salt diet. 3. Twenty-four hour urinary sodium excretion fell on the low salt diet from 163 to 29 mmol/day [standard error of the difference (SED)+/- 14, P less than 0.001]. Body weight decreased on salt restriction from 76.4 to 75.4 kg (SED +/- 0.33, P less than 0.05). Brachial mean arterial pressure fell by 6% (P less than 0.05), but right atrial pressure was unchanged. Renal vein plasma renin activity increased by 56% with sodium restriction (P less than 0.01), whereas arterial ANP concentrations fell by 39% (P less than 0.05). 4. Coronary sinus ANP levels fell from 417 to 268 pg/ml (SED +/- 74, P less than 0.05), whereas renal vein concentrations were unaltered. There was a 47% decrease in cardiac secretion of ANP in the low salt state (P less than 0.05). Net extraction of ANP across the kidney (about two-thirds) and renal clearance of ANP were unchanged on the low salt diet. Thus decreased plasma ANP with sodium restriction is due to reduced cardiac secretion. We determined the temporal effects of dietary sodium restriction on large elastic artery compliance and systolic blood pressure (SBP) in 12 untreated, older (64+/-2 years) men and women (6 each) with stage 1 systolic hypertension. After baseline measurements subjects were assigned to 4 weeks of low or normal sodium intake (randomized, crossover design). Urinary sodium excretion was reduced by 60% by the end of week 1 of sodium restriction (54+/-11 mmol/d, P<0.01) versus baseline (135+/-14). Compared with baseline (0.11+/-0.01 mm/mm Hg), carotid artery compliance was increased by 27% (to 0.14+/-0.02, P<0.05) at the end of week 1 of sodium restriction, attaining peak levels by week 2 (+46%, to 0.16+/-0.02, P<0.01). Similarly, supine resting brachial artery SBP was reduced by >5 mm Hg by week 1 of sodium restriction, attaining peak reductions by week 2 (-12 mm Hg, P<0.01 versus baseline). The 24-hour ambulatory SBP was approximately 3 mm Hg lower at week 1 of sodium restriction and approximately 6 mm Hg lower by week 2 (P<0.01 versus baseline). The reductions in resting SBP from baseline to week 2 of sodium restriction were strongly related to the corresponding increases in carotid compliance (r=0.80, P<0.01). Urinary sodium excretion, carotid artery compliance, and SBP were not different during normal sodium intake versus baseline. Other subject characteristics were not different across conditions. Sodium restriction rapidly improves large elastic artery compliance in older adults with stage 1 systolic hypertension. These improvements in central arterial compliance appear to be a key mechanism in the rapid normalization of SBP by sodium restriction in these patients. To examine the effects of sodium intake on insulin sensitivity, we performed euglycemic insulin clamp studies (40 mU.m-2.min-1) in eight healthy normotensive nondiabetic white males (age = 36 +/- 5 yr; wt = 66 +/- 3 kg) after 5 days on high (200 meq/day)- and low (10 meq/day)-sodium diets administered in random order. High sodium intake was associated with significantly greater urinary sodium excretion (160 +/- 7 vs. 8 +/- 2 meq/day; P < 0.0001), suppression of plasma aldosterone (7 +/- 3 vs. 38 +/- 6 ng/dl; P < 0.001) and renin (1.5 +/- 0.2 vs. 6.0 +/- 0.9 ng.ml-1.h-1; P < 0.005) levels, but no change in blood pressure (116 +/- 3/63 +/- 2 vs. 114 +/- 3/64 +/- 2 mmHg; P = not significant). The rate of glucose infusion during the clamp was significantly reduced during the high- vs. low-sodium diet (279 +/- 19 vs. 334 +/- 24 mg.m-2.min-1; P < 0.01). This impairment in insulin sensitivity was not related to changes in serum potassium, epinephrine, norepinephrine, cortisol, or growth hormone but was highly correlated with an increment in circulating free fatty acid levels during high sodium intake (r = 0.82, P < 0.05). These data suggest that 1) high sodium intake may exacerbate insulin resistance by increasing circulating free fatty acids, and 2) differences in sodium intake may influence measures of insulin sensitivity in other disease states. Dietary sodium restriction has a variety of effects on metabolism, including activation of the renin-angiotensin system. Angiotensin II has complex metabolic and cardiovascular effects, and these may be relevant to the effects of both nonpharmacological and pharmacological interventions in noninsulin-dependent diabetes mellitus (NIDDM). We have assessed the effect of dietary sodium restriction on insulin sensitivity and endogenous glucose production in eight normotensive patients with diet-controlled NIDDM who underwent hyperinsulinemic clamp studies in a randomized, double-blind, placebo-controlled cross-over protocol after two 4-day periods on sodium replete (160 mmol/day) and sodium deplete (40 mmol/day) diets. Mean +/- SD 24-h urinary sodium was 197 +/- 76.0 mmol (replete) and 67 +/- 19.5 mmol (deplete), P = 0.03. Insulin sensitivity was 42.0 +/- 11.3 mumol/kg.min (replete) and 37.0 +/- 11.6 mumol/kg.min (deplete), P = 0.04 (a reduction of 12%). Blood pressure was 130 +/- 21/78 +/- 11 mmHg (replete) and 128 +/- 12/73 +/- 10 mmHg (deplete). Dietary sodium restriction may result in a decrease in peripheral insulin sensitivity in normotensive patients with NIDDM, possibly via an elevation in prevailing angiotensin II concentrations. We gave sodium nitroprusside by intravenous infusion to 163 randomly selected patients during the first 24 hours after hospitalization for typical acute myocardial infarction, and we studied its effects on mortality at one week, on the incidence of cardiogenic shock, on clinical signs of left ventricular failure, and on peak levels of creatine kinase isoenzyme MB. A control group of 165 patients received standard medical treatment and infusion of 5 per cent glucose. The end point of the study was a significant reduction in mortality in the nitroprusside group; this was reached when five deaths had occurred in this group, as compared with 18 among the controls (P less than 0.05). The incidence of cardiogenic shock, clinical signs of left-heart failure, and mean peak levels of creatine kinase isoenzyme MB were all reduced (P less than 0.05). The results indicate that infusion of nitroprusside in the early phase of acute infarction limits complications, possibly by reducing infarct size. The drug was particularly effective in anterior-wall infarction. Nine white and 13 black hypertensive patients with normal serum creatinine were randomized to receive either 2 weeks of a low-salt (40 mEq Na+/d) or high-salt (200 mEq Na+/d) diet followed by 2 weeks of the other diet separated by a 1-week washout on their regular diet. The entire study was conducted in an outpatient setting with intensive dietary instruction and monitoring of blood pressure and 24-hour collections of urine for analysis. Urine electrolyte measurement showed that the patients were able to achieve only a modestly reduced (100 +/- 14 mEq Na+/24 h [mean +/- SEM]) low-salt diet as outpatients, while the higher-salt diet (236 +/- 22 mEq Na+/24 h) was more easily achieved. Eleven patients (8 black, 3 white) were classified as modestly salt sensitive on the basis of an increase or decrease in mean arterial pressure of > or = 3 mm Hg going from lower- to high- or high- to lower-salt diets, respectively. In the salt-sensitive patients, the increase in dietary salt intake increased glomerular filtration rate by 29% (71.2 +/- 6.6 to 85.8 +/- 7.3 mL.min-1.1.73 m2, P = .05), with no significant change in renal plasma flow (412.7 +/- 36.4 to 399.6 +/- 27.8 mL.min-1.1.73 m2). There were no changes in these parameters in the salt-resistant patients.(ABSTRACT TRUNCATED AT 250 WORDS) The aim of this study was to determine whether moderate restriction of dietary salt intake leads to an additional fall in blood pressure in treated hypertensive men who are asked to simultaneously reduce their usual alcohol intake. Sixty-three subjects entered an initial 2-week familiarization period during which they continued their usual alcohol intake and commenced a "low sodium" diet (less than 60 mmol/day) supplemented with 100 mmol sodium chloride per day as enteric-coated tablets. Subjects were then randomly assigned to either drink a low alcohol beer alone for a 4-week period (reducing their self-reported alcohol consumption from 537 to 57 ml/week) or to continue their usual alcohol intake (543 versus 557 ml/week). Within the low and normal alcohol intake groups, subjects were assigned to either a low or normal sodium intake. The low sodium groups continued the sodium-restricted diet but were switched to placebo sodium chloride tablets for the 4 weeks. This resulted in a fall in the 24-hour urinary sodium excretion from 144 to 69 mmol/day. The normal sodium groups continued the low sodium diet but kept taking 100 mmol/day of the sodium chloride tablets, and their urinary sodium excretion remained unchanged (125 versus 142 mmol/day). Regular antihypertensive therapy was continued throughout. Fifty-nine subjects completed the trial. In those who reduced their alcohol intake there was a fall in both systolic blood pressure (-5.4 mm Hg supine, p less than 0.01) and diastolic blood pressure (-3.2 mm Hg supine, p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS) 51 patients with mild essential hypertension (EH) were randomly divided into two groups; the first group (31 patients) was treated with 1 g. of oral calcium during a period of 8 weeks; the second group received a placebo. The treated with calcium showed a significant decrease in blood pressure (BP), the maximal reduction being of 6 mm Hg in the systolic pressure (SBP) and 3 mm in the diastolic (DBP) at the end of the 8th week. We found a substantial positive relationship between the decrease in SBP and seric renin activity (p less than 0.05), as well as a significant negative relationship (p less than 0.05) between DBP and the seric level of parathyroid hormone (PTH). During the administration of the oral calcium supplement, the BP decreased in an inverse proportion to the plasmatic renin and seric level of PTH. 1. Three groups of young patients with borderline hypertension were studied for a 12 months period. The first was on a free sodium diet while the second was on a low-salt diet. The third group of patients underwent acute salt loading. 2. After 12 months the group on free diet showed a significant increase of intralymphocytic sodium but no change in blood pressure was noted. Five patients who were re-checked after 24 months also had a significant increase in blood pressure. 3. Patients treated with a low-salt diet showed a significant decrease of both intralymphocytic sodium concentration and blood pressure. 4. After acute salt loading, borderline subjects with high intralymphocytic sodium showed a significant greater natriuresis whereas intralymphocytic sodium increased only in those subjects in whom it was initially normal. To evaluate the involvement of the renal dopaminergic system in the natriuretic responses to acute saline load in salt-resistant (SR) and salt-sensitive (SS) black normotensive (NT) and hypertensive (HT) subjects.
                We studied the relationship between the urinary excretion of dopa, dopamine (DA) and its metabolite DOPAC and the natriuretic responses to acute volume expansion (2 l NaCl 0.9% over 2 h) in 20 black NT subjects (12 SR and 8 SS) and 19 black HT subjects (10 SS and 9 SR). Subjects received a low salt (LS) diet (40 mmol sodium/day) for 1 week and a high salt (HS) diet (300 mmol sodium/day) for 1 week; the sequence of the dietary regimens was randomized. Comparisons were made between the results before the saline infusion (baseline) and the results 2 h after the infusion.
                In all the groups saline infusion induced significant increases in urinary volume (ml/4 h) of two- to three-fold and in urinary sodium excretion (mmol/4 h) of three- to ten-fold; these increases were significantly greater during the HS diet than during the LS diet. Saline infusion significantly increased the mean arterial pressure (MAP) by 5 mmHg in HT-SS subjects and by 4-5 mmHg in NT-SS subjects, but the MAP did not changed in the NT-SR and HT-SR groups. Under the LS diet, saline infusion changed the DA excretion (in nmol/4 h) by -49+/-89 in HT-SS subjects, by 17+/-52 in NT-SS subjects, by 235+/-72 in HT-SR subjects and by 220+/-86 in NT-SR subjects (P < 0.05 between SR and SS subjects). The saline infusion-induced changes in DA excretion correlated significantly with the increases in urinary sodium excretion (r = 0.71, P < 0.01) in the NT-SR and HT-SR subjects under the LS diet, but not in the SR groups on the HS diet nor in the SS groups (HT and NT) on either diet. Saline infusion significantly reduced the DA/dopa ratio in SS (NT and HT) but not SR (NT and HT) subjects, whereas the DA/DOPAC (dihydroxyphenylacetic acid) ratios were similar in all the groups.
                The urinary dopaminergic system may participate in the natriuretic responses to acute sodium load only in SR subjects (NT and HT) and only under LS diets, but not in SS subjects (NT and HT). This strongly suggests that black NT- and HT-SS subjects have an underlying impairment in the activity of the renal dopaminergic system which may be associated with a reduced decarboxylation of dopa into DA. Nitric oxide production is a homeostatic mechanism that may regulate blood pressure during salt loading. Salt-sensitive hypertension in animal models and in humans is characterized by increased blood pressure and decreased nitric oxide production after salt loading. It is not known if this impaired nitric oxide production is the result of hypertension or is a mechanism contributing to the blood pressure response to salt.
                The effects of salt loading on blood pressure, nitric oxide-mediated vasodilation and nitric oxide production were measured in 25 normotensive subjects after 6 days on either a high (400 mmol/day) or low (10 mmol/day) sodium, low nitrate diet. Mean arterial pressure increased during the high-salt diet [4 +/- 1 mmHg (mean +/- SEM)] in 12 subjects and remained unchanged or decreased (-4 +/- 1 mmHg) in 13 subjects. Plasma nitrite and nitrate, a measure of nitric oxide production, decreased significantly from 39 +/- 3.3 micromol/l during the low-salt diet to 22.4 +/- 2.4 micromol/l during the high-salt diet (P = 0.0001). However, changes in mean arterial pressure from low- to high-salt diet did not correlate with changes in plasma nitrite and nitrate (r = 0.14, P = 0.51). Forearm blood flow increased significantly (P <0.0001) in response to mental stress, a nitric oxide-mediated response, but was not affected by sodium intake (from 7.8 +/- 0.9 to 11.2 +/- 1.4 ml/min per 100 ml during low salt versus 8.5 +/- 1.2 to 10.4 +/- 1.3 ml/min per 100 ml during high salt,P = 0.3).
                Salt loading results in a decrease in nitric oxide production in both salt-sensitive and salt-resistant normotensive subjects, which is independent of changes in blood pressure and does not affect the nitric oxide-mediated vascular response to mental stress. In contrast to salt-resistant animal models, salt loading in healthy subjects does not increase nitric oxide production. Therefore, the increased blood pressure response to salt loading may occur through mechanisms other than nitric oxide, or salt-sensitive individuals are more sensitive to the reduced nitric oxide production that occurs after salt loading in both salt-sensitive and salt-resistant subjects. This study compared the relative efficacy of a once-daily niacin extended-release (ER)/lovastatin fixed-dose combination with standard doses of atorvastatin or simvastatin, with a special emphasis on relative starting doses. Subjects (n = 315) with elevated low-density lipoprotein (LDL) cholesterol and decreased high-density lipoprotein (HDL) cholesterol blood levels (defined as LDL cholesterol blood levels > or =160 mg/dl without coronary artery disease, or > or =130 mg/dl if coronary artery disease was present, and HDL cholesterol <45 mg/dl in men and <50 mg/dl in women) were randomized to atorvastatin, simvastatin, or niacin ER/lovastatin for 16 weeks. The primary efficacy variables were the mean percent change in LDL cholesterol and HDL cholesterol levels from baseline. After 8 weeks, the starting dose niacin ER/lovastatin 1,000/40 mg and the 10-mg starting dose atorvastatin both lowered mean LDL cholesterol by 38%. After 12 weeks, niacin ER/lovastatin 1,000/40 mg lowered LDL cholesterol by 42% versus 34% with the 20-mg starting dose of simvastatin (p <0.001). Niacin ER/lovastatin increased HDL cholesterol significantly more than atorvastatin or simvastatin at all compared doses (p <0.001). Niacin ER/lovastatin also provided significant improvements in triglycerides, lipoprotein(a), apolipoprotein A-1, apolipoprotein B, and HDL subfractions. A total of 6% of study subjects receiving niacin ER/lovastatin withdrew because of flushing. No significant differences were seen among study groups in discontinuance due to elevated liver enzymes. No drug-induced myopathy was observed. Niacin ER/lovastatin was comparable to atorvastatin 10 mg and more effective than simvastatin 20 mg in reducing LDL cholesterol, was more effective in increasing HDL cholesterol than either atorvastatin or simvastatin, and provided greater global improvements in non-HDL cholesterol, triglycerides, and lipoprotein(a). We aimed to test if fosinopril reduces urinary protein excretion and alleviates renal tubular damage in normotensive children with steroid-resistant idiopathic nephrotic syndrome (SRINS). We also aimed to evaluate whether there are changes in steady-state blood pressure and serum concentrations of serum angiotensin-converting enzyme (ACE) and plasma renin activity or angiotensin II (AT-II) in children under this treatment. Forty-five normotensive patients with SRINS were randomly divided into two groups. Group I was treated with fosinopril and prednisone for 12 weeks, while group II was treated with prednisone alone for the same duration. The values of 24-h urinary protein excretion were 1.25+/-0.64 vs 2.52+/-0.56 g/24 h (P<0.05), 1.16+/-0.45 vs 2.42+/-0.24 g/24 h (P<0.05), and 1.10+/-0.41 vs 2.05+/-0.46 g/24 h (P<0.05) in group I and group II patients, respectively, at 4, 8, and 12 weeks. Patients in group I showed lower serum concentrations of urinary retinol-binding protein and beta(2)-microglobulin (P<0.01) at the end of the study, but the patients' blood pressure and components of the renin-angiotensin system (RAS) had no change during treatment. The result suggested that fosinopril significantly reduced proteinuria and alleviated renal tubular damage, but did not influence blood pressure and components of systemic RAS in normotensive children with SRINS. Dietary salt restriction lowers blood pressure and has been advocated as a population-based strategy to reduce the cardiovascular morbidity associated with hypertension. However, the effect of lowering salt intake on metabolic vascular risk factors such as insulin resistance and levels of atherogenic lipids and fasting insulin is uncertain. We have studied the short-term effect of moderate dietary salt restriction on insulin resistance and serum lipids in 34 nonobese (body mass index [mean +/- SD] 23.4 +/- 1.8 kg/m2), normotensive young white men. Subjects were maintained on a low salt diet ( < 80 mmol/day) for the 2-week study period. In a randomized, cross-over, double-blind fashion, each subject also received 120 mmol of sodium chloride per day during one of the study weeks, and a matching placebo during the other. Insulin resistance, serum insulin, lipids, and blood pressure were measured in the fasting state at the end of each study week. Urinary sodium excretion (185 +/- 46 v 52 +/- 25 mmol/day, P < .001), serum sodium (141.2 +/- 1.2 v 140.1 +/- 1.3 mmol/L, P < .001) and body weight (75.4 +/- 9.1 v 75.0 +/- 9.3 kg, P < .05) were higher during the high salt than the low salt period. Serum creatinine was higher during the low salt period (100 +/- 8 v 90 +/- 9 mumols/L, P < .01). There was no difference in blood pressure, insulin resistance, serum insulin, C-peptide, total cholesterol, low density lipoprotein cholesterol, high density lipoprotein cholesterol or its subfractions, triglycerides, apolipoprotein A1, or apolipoprotein B between the high salt and low salt periods. We conclude that short-term, moderate dietary salt restriction does not adversely affect insulin sensitivity or levels of atherogenic lipids in normotensive nonobese men. We evaluated the effects of human atrial natriuretic peptide (hANP) during cardiopulmonary bypass (CPB).
                Forty patients undergoing coronary artery bypass grafting were investigated. A group of patients given hANP for 24 hours from the start of CPB (hANP group) was compared with a non-hANP group. Parameters examined were hemodynamics, urine volume, dosage of furosemide, respiratory index, pleural effusion, ANP, cyclic guanosine monophosphate, renin activity (renin), angiotensin-II, aldosterone, and glomerular filtration rate.
                Central venous pressure, systemic vascular resistance index, and pulmonary vascular resistance index were significantly lower in the hANP group than in the non-hANP group. The hANP group showed significantly higher levels of ANP, cyclic guanosine monophosphate, glomerular filtration rate, and respiratory index, and significantly lower levels of renin, angiotensin-II, aldosterone, and pleural effusion, as compared with the non-hANP group. The dosage of furosemide was significantly lower and the urine volume was significantly larger in the hANP group.
                hANP can satisfactorily compensate for the shortcomings of CPB by decreasing the peripheral vascular resistance, suppressing the renin-angiotensin-aldosterone system, and exerting a strong diuretic effect. We report a clinical study on the use of 7.2%, 2400 mOsm/L, hypertonic saline solution compared with gelatin in early postoperative period after coronary artery bypass surgery.
                Two groups (n = 10 each) received 5 ml/kg of either saline solution or gelatin over 1 hour. Cardiac index, central venous pressure, pulmonary capillary wedge pressure, systemic and pulmonary vascular resistance indices, arterial oxygen tension, plasma osmolarity, electrolytes, and urinary output were recorded before starting the infusion and subsequently at 10, 30, 60, 90, 120, 240 and 600 minutes. Plasma creatinine, urea, electrolytes, urinary volume, and sodium excretion were measured at 12 and 24 hours.
                There were no significant demographic or operative difference between the groups. Patients receiving saline solution had a larger diuresis at 12 (p = 0.0008) and 24 hours (p = 0.002), with less positive balance at 12 hours (p = 0.0008). The group receiving saline solution had better cardiorespiratory recovery with shorter extubation time (p = 0.033), and earlier increase in cardiac index with a positive correlation between plasma sodium content and cardiac index. Maximum increase in cardiac index (+31%) occurred at 60 minutes (p = 0.025) associated with 8% increase in plasma sodium content (r = 0.51, p = 0.01), without a concomitant rise in pulmonary capillary wedge pressure. The group receiving gelatin had a linear increase in cardiac index with increasing pulmonary capillary wedge pressure, reaching +16% from baseline by 90 minutes. Compared with the gelatin-treated group, patients receiving saline solution had unchanged systemic vascular resistance index but a significantly lower pulmonary vascular resistance index with a negative correlation to plasma sodium content. There was no difference in levels of urea and creatinine. No side-effect attributable to the use of saline solution was observed. To investigate the hemodynamic effects of a moderately low-salt diet in a 9-week, randomized, double-blind, crossover study in 20 hypertensive, ambulatory patients.
                All subjects followed a 9-week, low-salt diet. During this period, they received capsules containing either lactose or salt in 4-week treatment periods, separated by a 1-week washout period. Hemodynamic and biological parameters were evaluated on the day of randomization and at the end of weeks 4 and 9. We defined a low-sodium diet (LSD) as a salt-restriction period with lactose capsules, and a normal-sodium diet (NSD) as a salt-restriction period with capsular salt supplementation.
                Blood pressure was significantly lower during LSD compared with NSD. This fall in blood pressure was associated with a decrease in peripheral resistance in carotid and forearm circulation. Brachial artery diameter was larger during LSD whereas carotid artery diameter remained unchanged. The changes in brachial artery were: (1) not related to blood pressure changes; (2) positively related to age, and (3) negatively correlated with baseline intracellular sodium content.
                These results suggest that moderate low-salt restriction is capable of decreasing blood pressure and peripheral resistance in carotid and forearm circulation. The increase in brachial, but not carotid, artery diameter following salt restriction suggests a difference in salt dependence among different arteries. Hypertension remains the most common cardiovascular risk factor in developing countries, yet the majority of patients have no access to pharmacological therapy. Population-wide preventive strategies, such as salt restriction, are an attractive alternative, but experience in resource-poor settings is limited. To address this question, we conducted a randomized crossover study of salt restriction in adults living in Nigeria and Jamaica in order to estimate the mean blood pressure (BP) response. After a 4-week run-in period to determine willingness to adhere to a low-salt diet, 56 Jamaicans and 58 Nigerians completed an 8-week crossover study of low-salt and high-salt intake. Baseline BPs were in the normotensive range (systolic=125 mmHg in Jamaica, 114 mmHg in Nigeria). Baseline urinary sodium excretion was 86.8 and 125.6 mEq/day in Nigeria and Jamaica, respectively. The mean difference between urinary sodium excretion at baseline and at the end of the 3-week low-sodium phase was 33.6 mEq/day in Nigeria and 57.5 mEq/day in Jamaica. During the high-sodium phase, mean change in urinary sodium excretion from baseline to week 3 was 35.0 and 5.5 mEq/day in Nigeria and Jamaica, respectively. The mean change in systolic BP ('high' vs 'low' sodium phase) was approximately 5 mmHg in both groups. This study suggests that the efficacy of sodium reduction in developing countries equals those noted in more affluent cultures. If promoted on a wide scale, sodium reduction could be used to treat persons with established hypertension, and more importantly, to prevent age-related increases in BP in poor communities. An increase of some serum lipid fractions has been documented in normotensive healthy volunteers and patients with essential hypertension during acute drastic restriction of salt intake. To clarify the potential role of vasopressor systems, particularly the sympathetic system, in the lipid changes induced by salt restriction, we compared fasting serum lipids, glucose, insulin, and C-peptide levels in 16 normotensive healthy volunteers during 7 days of high (200 mmol/day) and 7 days of low (20 mmol/day) salt intake. The individuals were examined on either placebo or on the alpha 1-adrenergic blocker doxazosin (2 mg/day). The study was carried out using a single blind parallel group random order design with two arms of treatment. In the volunteers on placebo, total cholesterol (corrected for hemoconcentration) was significantly higher (P < .01) during low salt intake. The same was true for LDL-cholesterol, whereas HDL-cholesterol and triglycerides did not change with salt intake. The lipid changes, and, in parallel, the changes of hemoconcentration indicators, were more pronounced after 2 days than after 7 days of low salt intake. The rise of total and LDL-cholesterol on low salt was blunted after alpha 1-adrenergic blockade with doxazosin. Fasting glycemia was similar on low salt and high salt, respectively, but in placebo treated volunteers, C-peptide levels were significantly (P < .01) higher on low, rather than high, salt intake. alpha 1-Adrenergic blockade with doxazosin attenuated the rise of C-peptide levels on low salt. The results confirm previous findings that levels of total cholesterol and LDL-cholesterol change inversely with salt intake in normotensive healthy volunteers.(ABSTRACT TRUNCATED AT 250 WORDS) The effect of dietary composition on blood pressure is a subject of public health importance. We studied the effect of different levels of dietary sodium, in conjunction with the Dietary Approaches to Stop Hypertension (DASH) diet, which is rich in vegetables, fruits, and low-fat dairy products, in persons with and in those without hypertension.
                A total of 412 participants were randomly assigned to eat either a control diet typical of intake in the United States or the DASH diet. Within the assigned diet, participants ate foods with high, intermediate, and low levels of sodium for 30 consecutive days each, in random order.
                Reducing the sodium intake from the high to the intermediate level reduced the systolic blood pressure by 2.1 mm Hg (P<0.001) during the control diet and by 1.3 mm Hg (P=0.03) during the DASH diet. Reducing the sodium intake from the intermediate to the low level caused additional reductions of 4.6 mm Hg during the control diet (P<0.001) and 1.7 mm Hg during the DASH diet (P<0.01). The effects of sodium were observed in participants with and in those without hypertension, blacks and those of other races, and women and men. The DASH diet was associated with a significantly lower systolic blood pressure at each sodium level; and the difference was greater with high sodium levels than with low ones. As compared with the control diet with a high sodium level, the DASH diet with a low sodium level led to a mean systolic blood pressure that was 7.1 mm Hg lower in participants without hypertension, and 11.5 mm Hg lower in participants with hypertension.
                The reduction of sodium intake to levels below the current recommendation of 100 mmol per day and the DASH diet both lower blood pressure substantially, with greater effects in combination than singly. Long-term health benefits will depend on the ability of people to make long-lasting dietary changes and the increased availability of lower-sodium foods. To investigate the effect of cyclosporine A (CsA; Sandimmun Neoral) on systemic and renal hemodynamics, tubular function, and sodium excretion in healthy volunteers. Furthermore, we studied whether CsA enhances the systemic and renal hemodynamic sensitivity to norepinephrine.
                Eighteen healthy volunteers were administered 10 mg/kg CsA or placebo capsules in a double-blind fashion. The mean arterial blood pressure (MAP), renal vascular resistance (RVR), glomerular filtration rate (GFR), and renal clearances of lithium (CLi) and sodium (CNa) were measured for 8 h after ingestion of the capsules. Norepinephrine (2 microg/kg per h) was infused intravenously for 1.5 h into nine subjects.
                CsA increased the MAP by 17+/-2 mmHg. The GFR decreased by 18+/-2% (P < 0.001) and the RVR increased by 37+/-4% (P< 0.001) after ingestion of CsA. The CsA-induced increase in MAP preceded the CsA-induced fall in GFR. The rise in MAP was followed by an early 35+/-8/0 increase in CNa (P < 0.001). At the end of the 8 h study period, CNa decreased by 25+/-7% (P < 0.001). Using CLi, it was found that the initial natriuresis had been caused by a relative decrease both in proximal and in distal tubular reabsorption of sodium, whereas the late sodium retention was secondary to the CsA-induced fall in GFR. Infusion of norepinephrine increased the MAP, RVR, and filtration fraction, and decreased the renal plasma flow, without CsA having any additional effect.
                It was demonstrated that a single oral dose of CsA caused a rise in blood pressure and transient natriuresis, followed by a fall in GFR and antinatriuresis. Thus, the present study confirms and extends earlier observations that renal dysfunction and sodium retention are not the initiating events in CsA-induced hypertension. The study also affords evidence suggesting that such rises in blood pressure are not mediated by an increased sensitivity to norepinephrine. The new angiotensin converting enzyme inhibitor enalapril (MK-421), was given in a single daily dose of 20 mg to 53 patients with uncomplicated essential hypertension. Its effects were compared with those of a placebo given to 47 patients on a double-blind randomized basis. The blood pressure was measured in all patients by a physician, using a mercury sphygmomanometer, and by an automatic device in the absence of the physician. After 15 days of treatment, enalapril induced a significant reduction in systolic blood pressure (161.4 +/- 13 versus 145.1 +/- 15, p less than 0.001) and in diastolic blood pressure (103.3 +/- 6 versus 92.9 +/- 8, p less than 0.001) measured by the physician. The magnitude of the fall in blood pressure was identical after 30 days of active treatment. The reduction in blood pressure induced by enalapril was similarly detected by both methods of measurement, despite the fact that blood pressure values were higher when measured by the physician. A placebo effect was observed with the physician's values that was not present with the automatically recorded values. A very significant correlation between blood pressure values obtained by these two methods was observed. However, among nine of 53 patients treated with enalapril, a difference in the decrease of blood pressure of 10 mm Hg or more was noted between the two methods of measurement. The decrease in blood pressure occurred with no change noted in the pulse rate or orthostatic hypotension. Plasma renin activity increased after treatment. No changes were observed in creatinine clearance and plasma electrolyte levels. Hydroxymethylglutaryl coenzyme A (HMG-CoA) reductase inhibitors are the drugs of choice in heterozygous familial hypercholesterolemia (FH), which has a high risk of ischemic heart disease. An open-label study was conducted to test the efficacy and safety of atorvastatin, a new synthetic HMG-CoA reductase inhibitor in proven FH. After a 4-week placebo phase, 22 subjects were randomized to either 80 mg atorvastatin at night (n = 11) or 40 mg twice a day for 6 weeks. The two dosage groups were well matched and had no difference in lipoprotein responses. After 6 weeks, the LDL cholesterol concentration was reduced by 57%, from 8.16 +/- 1.15 to 3.53 +/- 0.99 mmol/L (P < .001). The total cholesterol concentration decreased from 9.90 +/- 1.32 to 5.43 mmol/L (P < .001). HDL cholesterol concentration increased from 1.19 +/- 0.31 to 1.49 +/- 0.43 mmol/L (P < .001). Triglyceride concentrations decreased from 1.34 +/- 0.66 to 0.88 +/- 0.36 mmol/L (P < .01). Three subjects had single, transient increases of serum transaminase of up to twice the upper limit of normal. Apolipoprotein B concentration decreased significantly by 42%. Changes in apolipoproteins AI and (a) were not statistically significant. Nondenaturing gradient gel electrophoresis revealed increases in the size of smaller LDL particles in four subjects. Plasma fibrinogen concentration increased by 44%. The drug was well tolerated. One subject withdrew for personal reasons. Atorvastatin is a powerful and safe lipid-modifying agent for LDL cholesterol; it also modifies HDL cholesterol and triglyceride concentrations, and may suffice as a single agent for many subjects with heterozygous FH. To evaluate the magnitude and cause of metabolic acidosis after infusion of 7.5% sodium chloride 6% dextran 70.
                Randomized, prospective clinical study.
                University hospital.
                Two groups of 14 patients each, undergoing repair of abdominal aortic aneurysm.
                Patients were randomly assigned to receive either 250 mL of hypertonic saline dextran (HSD) or a conventional fluid regimen with 250 mL of hydroxyethyl starch in normal saline solution (H-NS) during the period of aortic clamping. Additionally, normal saline was used in both groups to reach a target pulmonary artery occlusion pressure of 15-18 mmHg. pH, Paco2, and serum concentrations of sodium, potassium, magnesium, calcium, chloride, lactate, albumin, and phosphate were measured. Strong ion difference was calculated as (sodium + potassium + magnesium + calcium) - (chloride + lactate). The amount of weak plasma acid was calculated.
                The infusion of HSD resulted in an immediate large increase in serum sodium (19 mmol/L) and chloride (22 mmol/L), whereas the infusion of H-NS led only to mild increases in serum sodium (3 mmol/L) and chloride (6 mmol/L). Both HSD and H-NS caused concomitant and equal decreases in the amount of weak plasma acid, strong ion difference, and pH (7.28-7.30). The reduction of bicarbonate was also identical and proportional to the extent of dilution due to infusion of HSD and H-NS. This induced metabolic acidosis was corrected spontaneously in both groups 24 hrs after surgery.
                Both the intravenous administration of 7.5% sodium chloride and the conventional fluid regimen with saline-based 6% hydroxyethyl starch solution resulted in a metabolic acidosis of equal extent. This suggests dilution of plasma buffers or a decrease in strong ion difference to be the primary cause of metabolic acidosis. We have previously reported that modest dietary sodium restriction, as advocated in management guidelines for diabetes, may reduce insulin sensitivity. It has since been suggested that this effect may be mediated via cross-talk between insulin and angiotensin II (AII)-stimulated intracellular second messengers. In order to assess the effect of 5 days of modest sodium restriction (to <80 mmol/day target sodium intake) on insulin sensitivity, 15 healthy males underwent a double-blind, placebo-controlled, randomized, cross-over euglycaemic hyperinsulinaemic clamp study. One phase was supplemented with sodium tablets and the other with matched placebo. Insulin sensitivity (M) was reduced during dietary sodium restriction [median M value, 10.2 mg/kg per min (interquartile range 9.50-13.85) versus 12.8 mg/kg per min (interquartile range 9.60-14.30), P <0.05]. To elucidate potential mechanisms that may explain this observation, we investigated the effect of AII on insulin action in isolated adipocytes obtained from healthy females. No effect of AII on insulin-mediated glucose transport or suppression of lipolysis was observed. In conclusion, despite the observation that dietary sodium restriction was associated with a median 15% reduction in insulin sensitivity, we found no evidence of a direct effect of AII on insulin action in human adipocytes.
Sodium reduction resulted in a 1% decrease in blood pressure in normotensives, a 3.5% decrease in hypertensives, a significant increase in plasma renin, plasma aldosterone, plasma adrenaline and plasma noradrenaline, a 2.5% increase in cholesterol, and a 7% increase in triglyceride. In general, these effects were stable in studies lasting for 2 weeks or more.