title: Involvement of Kallikrein in the Antihypertensive Response to Furosemide in Essential Hypertension Ticrynafen and hydrochlorothiazide in hypertension TORAFIC study protocol: torasemide prolonged release versus furosemide in patients with chronic heart failure Efficacy of a fixed-dose combination of 40 mg penbutolol with 6 mg piretanide in the treatment of mild to moderate hypertension: a double-blind study against placebo. Atenolol or propranolol in hypertensive patients poorly controlled on captopril and frusemide. A randomized trial of saline hydration to prevent contrast nephropathy in chronic renal failure patients. Vasopressin-2-receptor antagonism augments water excretion without changes in renal hemodynamics or sodium and potassium excretion in human heart failure. Effect of intravenous enalaprilat in moderate and severe systemic hypertension. Effect of furosemide on left ventricular mass in non-dialysis chronic kidney disease patients: a randomized controlled trial. Piretanide in the treatment of essential hypertension. A double-blind comparison versus placebo. Dosage dependent hormonal counter regulation to combination therapy in patients with left ventricular dysfunction. The Eurevie Study: contrasting effect of piretanide and thiazides in mild to moderate hypertension. [Efficacy of monotherapy with 15 antihypertensive agents in treating essential hypertension assessed by 24-hour ambulatory blood pressure monitoring]. A multicenter, randomized, double-blind, placebo-controlled study of tolvaptan monotherapy compared to furosemide and the combination of tolvaptan and furosemide in patients with heart failure and systolic dysfunction. Neurohormonal effects of furosemide withdrawal in elderly heart failure patients with normal systolic function. A randomized double-blind clinical trial of xipamid and hydrochlorothiazide in essential hypertension. Comparison of the effects of torasemide and furosemide in nonazotemic cirrhotic patients with ascites: a randomized, double-blind study. BIOCHEMICAL AND HÆMATOLOGICAL CHANGES INDUCED BY TIENILIC ACID COMBINED WITH PROPRANOLOL IN ESSENTIAL HYPERTENSION Propranolol and tienilic acid in essential hypertension. Fluctuations in blood lipid levels during furosemide therapy: a randomized, double-blind, placebo-controlled crossover study. Role of renin classification for diuretic treatment of black hypertensive patients. Antihypertensive and biochemical effects of indacrinone enantiomers. A Double-Blind Multicentre Study of Piretanide and Hydrochlorothiazide in Patients with Essential Hypertension Furosemide in essential hypertension. A statistical analysis of three double-blind studies. [Evaluation of cicletanine efficiency and tolerance in hypertensive patients treated with beta-blockaders]. Experience with Once-Daily and Twice-Daily Slow-Release Frusemide in Hypertension Efficacy of a low fixed-dose combination of penbutolol with piretanide in the treatment of mild to moderate hypertension: a double-blind study against placebo. A randomised placebo controlled trial of loop diuretics in moderate/severe pre-eclampsia, following delivery. The effects of adding torasemide to standard therapy on peak oxygen consumption, natriuretic peptides, and quality of life in patients with compensated left ventricular systolic dysfunction. Comparison of the antihypertensive activities of xipamide and chlorthalidone: a double-blind, randomized, crossover trial. Double-blind, placebo-controlled trial of alternate-day furosemide therapy in infants with chronic bronchopulmonary dysplasia. Usefulness of piretanide plus ramipril for systemic hypertension: a multicenter trial. Treatment of benign essential hypertension with frusemide in different doses. The effect of bendrofluazide and frusemide on the ventilatory response to carbon dioxide and hypoxia in normal man. A double-blind study of tienilic acid with two year follow-up of patients with mild to moderate essential hypertension. [Comparison of the clinical usefulness of diuretics in elderly and younger essential hypertension--double blind trial using tripamide]. Effects of angiotensin and angiotensin blockade on coronary circulation and coronary reserve.
abstract: Summary : Twelve white men with essential hypertension were treated for 1 month in r and omized order with either placebo or low-dose furosemide ( 40 mg/day ) and compared to 22 race , age- , and diet-matched normal controls .  Furosemide therapy significantly reduced mean arterial pressure ( 108.6 ± 2.4 vs. 101.0 ± 2.7 mm Hg . p < 0.02 ) in association with a significant increase in 24 hr urinary kallikrein activity ( 7.9 ± 1.8 vs. 13.4 ± 2.8 esterase units/24 hr . p < 0.02 ) . Normal controls on no therapy excreted 19.4 ± 2.6 esterase units/24hr of urinary kallikrein activity , significantly greater than hypertensives on placebo ( p < 0.01 ) but not hypertensives on furosemide ( p < 0.01 ) . The decrease in mean arterial pressure and the increase in urinary kallikrein activity induced by furosemide were not associated with a demonstrable change in renal hemodynamics . plasma renin activity , or plasma aldosterone concentration , but they were associated with a significant increase in intravascular volume ( 5.876 ± 339 vs. 6.808 ± 346 ml . p < 0.01 ) . A significant ( p < 0.05 ) inverse correlation between mean arterial pressure and urinary kallikrein activity suggests a possible role for the kallikrein-kinin system in the antihypertensive mechanism of furosemide In a double‐blind study , 28 patients having mild to moderate essential hypertension were r and omly assigned to a 6‐week regimen of ticrynafen , hydrochlorothiazide , or placebo .  Blood pressure fell after ticrynafen and hydrochlorothiazide .  Serum uric acid fell strikingly with ticrynafen whereas it rose with hydrochlorothiazide .  Serum potassium declined very little with ticrynafen ; much less than with hydrochlorothiazide . Serum creatinine and blood urea nitrogen rose slightly more with ticrynafen than with hydrochlorothiazide . There were no clinical adverse effects to either of the medications . Ticrynafen appears to be an effective antihypertensive with a substantial hypouricemic effect Loop diuretics , such as torasemide and furosemide , are important agents in the treatment of chronic heart failure . Beneficial effects of torasemide immediate-release formulation beyond diuresis have been documented as the ability of this compound to inhibit myocardial synthesis and deposition of collagen type I in patients with chronic heart failure . In addition , torasemide-treated patients , but not furosemide-treated patients , showed decreased serum concentrations of the C-terminal propeptide of procollagen type I , a biochemical marker of myocardial fibrosis . The aim of the TORAFIC study is to test the efficacy of torasemide prolonged-release formulation ( PR ) in reducing myocardial fibrosis in chronic heart failure in a large , r and omized clinical trial . Methods : This prospect i ve , Phase IV , r and omized , blinded end point , active-controlled clinical trial will r and omize 142 patients with chronic heart failure in New York Heart Association functional class II – IV to 8 months treatment with either torasemide-PR ( 10–40 mg daily ) or furosemide ( 40–160 mg daily ) . The primary objective is to test the hypothesis that torasemide-PR is superior to furosemide in reducing myocardial fibrosis . The primary outcome measure is the difference in the change of serum propeptide of procollagen type I concentration from the initial to the final visit between both study groups . Secondary outcome measures include all efficacy variables related to heart failure ( signs and symptoms , ECG , echocardiogram and serum levels of N-terminal brain natriuretic propeptide ) . Secondary safety variables are heart rate , blood pressure , laboratory data , adverse events , cardiovascular events ( hospital admission , emergency department visits ) and quality of life ( Minnesota question naire ) . Discussion : This trial will test whether torasemide-PR possesses antifibrotic properties , which may provide an additional benefit beyond diuresis in patients with chronic heart failure The antihypertensive efficacy and tolerability of a fixed-dose combination containing 40 mg penbutolol ( a beta-blocking agent ) and 6 mg piretanide ( a diuretic ) in comparison to placebo was investigated in a double-blind , crossover study in 20 patients with mild to moderate essential hypertension . After a 1-week period on placebo , patients were allocated at r and om to receive 1 tablet daily for 4 weeks of either the combination preparation or placebo and were then crossed over to the alternative medication for a further 4 weeks . The reduction in systolic and diastolic blood pressure both at rest , during maximal ergometric exercise and isometric word load , and also in the diurnal blood pressure profile over 24 hours was significantly greater in the group treated with the fixed-dose combination than in the placebo group . Pulse rate was also decreased to a greater extent . Mean diastolic blood pressure before exercise was reduced to normal ( 85.5 mmHg ) after 4-weeks ' treatment with the fixed-dose combination . Biochemical , haematological and urinary parameters showed no clinical ly relevant changes after either treatment . One patient complained of transient dizziness during treatment with the fixed-dose combination . No patient withdrew prematurely from the study because of side-effects Eighteen patients whose clinic blood pressure ( BP ) remained over 95 mmHg despite treatment with captopril 50 mg twice daily plus frusemide 40 mg twice daily were r and omised in a crossover study to four weeks ' treatment with once daily atenolol 100 mg , slow release propranolol 160 mg or placebo . The reduction in BP on atenolol was superior to that on both propranolol and placebo . The mean supine BP 24 hours post dosing were 177/110 mmHg ( placebo ) , 173/109 mmHg ( propranolol ) and 164/100 mmHg ( atenolol ) . The corresponding mean heart rates were 77 bpm ( placebo ) , 63 bpm ( propranolol ) and 62 bpm ( propranolol ) and 62 bpm ( atenolol ) . The difference in hypotensive efficacy between atenolol and propranolol is not readily explained but our study shows that atenolol has a clinical ly useful supplementary effect on BP . Refractory hypertension remains an important clinical problem and further studies are required to establish the optimum combination of drugs that should be used with captopril in order to achieve ' target ' BP in patients with moderate to severe hypertension BACKGROUND Contrast nephropathy ( CN ) is a common cause of renal dysfunction that may be prevented by saline hydration and by drugs such as theophylline or furosemide . Whether oral saline hydration is as efficient as intravenous saline hydration is unknown . The preventive efficacy of theophylline and furosemide for CN remains controversial . The purpose of the current study was to evaluate the efficacy of oral saline hydration and of intravenous saline hydration plus theophylline or furosemide for the prevention of CN . METHODS We prospect ively studied 312 patients with chronic renal failure ( serum creatinine 201+/-81 micromol/l , Cockcroft clearance 37+/-12 ml/min/1.73 m(2 ) ) , who were undergoing various radiological procedures with a non-ionic , low osmolality contrast agent . Patients were r and omly assigned to four arms . In arm A , patients received 1 g/10 kg of body weight/day of sodium chloride per os for 2 days before the procedure . In arm B , patients received 0.9 % saline intravenously at a rate of 15 ml/kg for 6 h before the procedure . In arm C , patients received the same saline hydration as in arm B plus 5 mg/kg theophylline per os in one dose 1 h before the procedure . In arm D , patients received the same saline hydration as in arm B plus 3 mg/kg of furosemide intravenously just after the procedure . RESULTS Patients were well-matched with no significant differences at baseline in any measured parameters .  Acute renal failure , defined as an increase in serum creatinine of 44 micromol/l ( 0.5 mg/dl ) , occurred in 27 out of 312 patients ( 8.7 % ) . There was no significant difference between the rate of renal failure in the different arms of the study : five out of 76 ( 6.6 % ) in arm A , four out of 77 ( 5.2 % ) in arm B , six out of 80 ( 7.5 % ) in arm C and 12 out of 79 ( 15.2 % ) in arm D. No patient had fluid overload or a significant increase in blood pressure in the 2 days following the radiological procedure . The independent predictors of CN were diabetes mellitus , high baseline serum creatinine and high systolic blood pressure . CONCLUSIONS Oral saline hydration was as efficient as intravenous saline hydration for the prevention of CN in patients with stage 3 renal diseases . Furosemide and theophylline were not protective Diuretics are frequently required to treat fluid retention in patients with congestive heart failure ( CHF ) . Unfortunately , they can lead to a decline in renal function , electrolyte depletion , and neurohumoral activation . Arginine vasopressin ( AVP ) promotes renal water reabsorption via the V2 receptor , and its levels are increased in CHF . This study was design ed to assess the effects of a single oral dose of tolvaptan , a selective V2-receptor blocker , in the absence of other medications , on renal function in human CHF and to compare this to the effects of a single oral dose of furosemide . We hypothesized that V2-receptor antagonism would yield a diuresis comparable to furosemide but would not adversely affect renal hemodynamics , plasma electrolyte concentration , or neurohumoral activation in stable human CHF . Renal and neurohumoral effects of tolvaptan and furosemide were assessed in an open-label , r and omized , placebo-controlled crossover study in 14 patients with NYHA II-III CHF . Patients received placebo or 30 mg of tolvaptan on day 1 and were crossed over to the other medication on day 3 . On day 5 , all subjects received 80 mg of furosemide . Tolvaptan and furosemide induced similar diuretic responses . Unlike tolvaptan , furosemide increased urinary sodium and potassium excretion and decreased renal blood flow .  Tolvaptan , furosemide , and placebo did not differ with respect to mean arterial pressure , glomerular filtration rate , or serum sodium and potassium . We conclude that tolvaptan is an effective aquaretic with no adverse effects on renal hemodynamics or serum electrolytes in patients with mild to moderate heart failure The antihypertensive effect and tolerability of enalaprilat , an intravenously administered angiotensin converting enzyme inhibitor , was studied in 65 patients with moderate or severe hypertension . In this r and omized , double-blind study , enalaprilat was compared with placebo in 42 ( 22 enalaprilat , 20 placebo )  moderate hypertensive ( diastolic blood pressure [ BP ] 100 to 114 mm Hg ) patients . It was compared with furosemide in 23 ( 12 enalaprilat , 11 furosemide ) severe hypertensive ( diastolic BP 115 to 130 mm Hg ) patients . Enalaprilat ( 1.25 or 5.0 mg ) , placebo ( 5 % dextrose ) or furosemide ( 40 or 80 mg ) was given every 6 hours intravenously up to 48 hours . In the moderate hypertension stratum , the mean supine diastolic BP was significantly ( p less than or equal to 0.01 ) reduced from baseline at all timepoints in the enalaprilat group . These diastolic BP reductions were significantly ( p less than or equal to 0.01 ) greater in the enalaprilat group than the placebo at 1 to 24 hours ( -12 vs -4 mm Hg ) , with 59 % of the patients responding to enalaprilat compared with 30 % of the patients responding to placebo . An even greater reduction ( p less than or equal to 0.01 ) was seen at 25 to 48 hours ( -14 vs -7 mm Hg , with 73 % enalaprilat vs 58 % placebo responders ) . Significant ( p less than or equal to 0.01 ) reductions in mean , supine systolic BP were also seen at 1 to 24 hours ( -22 vs -2 mm Hg ) and 25 to 48 hours ( -24 vs -8 mm Hg ) during the 48 hours of the double-blind treatment phase in the enalaprilat group compared with placebo . ( ABSTRACT TRUNCATED AT 250 WORDS BACKGROUND In chronic kidney disease ( CKD ) , loop diuretics correct volume-dependent hypertension , but their effect on left ventricular mass index ( LVMI ) is unknown . METHODS Forty hypertensive CKD patients ( estimated creatinine clearance 60 - 15 mL/min/1.73 m² ) , treated with renin-angiotensin system ( RAS ) inhibitors , were r and omized to  receive furosemide or non-diuretic antihypertensive treatment ( control group )  . Office blood pressure ( BP ) < 130/80 mmHg was pursued in both groups . Primary end point was the reduction of LVMI after 52 weeks . Secondary aims were to verify safety related to furosemide treatment and its effects on ambulatory and clinic BP and body fluid volumes . RESULTS Office BP similarly declined in the furosemide group ( from 161 ± 14/80 ± 10 to 139 ± 14/74 ± 8 mmHg ) and in controls ( from 159 ± 16/81 ± 10 to 137 ± 16/75 ± 10 mmHg ) . We detected a greater reduction ( P = 0.013 ) of LVMI in patients receiving furosemide ( -7.9 , IQR from -15.8 to -1.4 g/h(2.7 ) ) than in controls ( 0.0 , IQR from -6.2 to + 9.5 g/h(2.7 ) , P = 0.013 ) . Bio-impedance analysis -derived extracellular water ( ECW ) significantly decreased in furosemide-treated patients ( from 18.7 ± 3.9 to 17.7 ± 3.3 L ) while remained unchanged in the control group ( from 19.5 ± 2.2 to 19.6 ± 1.9 L ) . Absolute change of LVMI correlated with changes of ECW in furosemide-treated patients ( r = 0.458 , P = 0.042 ) but not in controls . In the furosemide group , no patient experienced side effects requiring drug withdrawal . CONCLUSIONS In hypertensive CKD patients treated with RAS inhibitors  , add-on furosemide efficaciously reduces LVMI independently from BP changes . The effect is possibly mediated by better control of volume expansion In a r and omized , double-blind parallel group study the 24-hour hypotensive effect of piretanide and its influence on biochemical variables were compared with those of placebo in patients with mild to moderate essential hypertension . Sixty patients entered the study , all of whom met the inclusion criteria ( RRdiast between 95 and 120 mmHg ) . There was no drop-out during the study , so that the results of all 60 patients were statistically analysed . Piretanide produced a significant reduction of both systolic and diastolic blood pressure over 24 hours which was evident at four weeks and was maintained and further enhanced over the ensuing trial period . A mean maximal fall ( at 12 weeks ) of 10.7 % ( BPdiast supine ) was observed . Placebo tablets did not produce any clinical ly relevant changes in systolic blood pressure , whereas a slight decrease was seen in diastolic blood pressure . This blood pressure reduction was significantly less in the placebo group than in the piretanide group at the end of the study ( weeks 10 and 12 ) . Dose doubling was needed in 13 of the 30 patients in the piretanide group , whereas as many as 20 out of 30 patients needed dose doubling in the placebo group . Pulse rate did not change relevantly during the trial in either group . A slight reduction in body weight was observed in the piretanide group . The mean values of serum potassium and sodium showed a slight decrease but remained within the normal range during the study period . A small increase in serum phosphorus was noted . None of these changes required any specific measures . ( ABSTRACT TRUNCATED AT 250 WORDS UNLABELLED The present study attempts to assess the efficacy combination therapy for heart failure . Genuine dose-response studies on combination therapy are not available and published studies involved adding one drug on top of ' usual treatment ' . Sixteen different dosage combinations of tr and olapril and bumetanide was tested in a double blind , double placebo-controlled , r and omized , multiple cross-over study in a 16 times six balanced incomplete Latin square design . Patients reported optimal quality of life on the sub maximal dose bumetanide . Bumetanide decreased left ventricular function and increased heart rate and plasma noradrenaline in a dose dependent manner . Doses of bumetanide of more than 0.5 mg , given twice daily significantly decreased the quality of life and increased diuresis . Weight loss was maximal on 0.5 mg bumetanide twice daily . Tr and olapril significantly reduced systolic blood pressure with the maximal effect at 0.5 mg daily . Both drugs significantly increased renin concentration with a significant potentiating interaction . It was not possible to detect beneficial effects of combination therapies . The optimal dosage of Bumetanide appeared to be 0.5 mg twice daily based on its effect on quality of life and weight loss . Estimated by the reduction in systolic blood pressure the optimal dosage of Tr and olapril appeared to be 0.5 mg once daily . CONCLUSIONS It appears that patients should be given less than the usually recommended dosages . Patients may be treated with a low dose loop diuretic , if signs of water retention are present or if symptomatic relief is desired UNLABELLED This study compares the loop diuretic piretanide 6 mg in a slow-release formulation ( PIR ) with hydrochlorothiazide 25 mg ( HCT ) and the fixed combination altizide 15 mg-spironolactone 25 mg ( ALT-SP ) in hypertension . 1105 mild to moderate hypertensive patients entered a three-week placebo wash-out period ; 899 were r and omized in a 6-month , double-blind , parallel group treatment phase ; 800 completed the study . Primary end-points ; serum potassium concentration and quality of life at one month ; secondary end-points : ionic , renal and metabolic variables ; blood pressure ( BP ) measurements . HCT and ALT-SP were compared only to PIR using Dunnett 's or chi 2 tests . RESULTS No difference was found for the overall quality of life . No change of serum potassium concentration at one month was found in PIR while small decreases were detected with ALT-SP ( -0.1 mM ) and HCT ( -0.26 mM ) . Serum creatinine concentration increased significantly in ALT-SP when compared to PIR . All the drugs were effective in reducing BP : HCT had a higher rate of responders than PIR with similar mean BP falls and ALT-SP induced greater falls in blood pressure . CONCLUSION PIR proves to be a potent antihypertensive drug without significant effect on serum electrolytes , plasma glucose and lipids . HCT was slightly more potent but induced a fall in serum potassium concentration with a significant risk of hypokalaemia . The addition of SP to ALT led to a more potent diuretic with a higher level of serum potassium and plasma creatinine disturbances OBJECTIVE To evaluate the efficacy of the monotherapy of 15 agents in treating essential hypertension . METHODS After 2-week wash-out , a total of 370 patients with seated diastolic blood pressure 95 - 114 mmHg and seated systolic blood pressure < 180 mmHg were r and omized to different therapeutic groups .  24-hour ambulatory blood pressure monitoring was performed before medication and at the end of 8 weeks . RESULT All the agents significantly reduced the 24 hour mean blood pressures after treatment except doxazosin , terazosin , and torasemide . CONCLUSION The result suggested that the angiotensin-converting enzyme inhibitors , angiotensin II receptor blockers , beta-blockers and long-acting calcium antagonists were effective in treating essential hypertension , while the low-dose doxazosin , terazosin and torasemide can be used for combination therapy but not for monotherapy BACKGROUND Increased vasopressin levels may be present in patient with chronic heart failure ( HF ) and contribute to pathophysiology through effects on the vasopressin V2 receptor . The presence of background diuretic therapy may confound evaluations of vasopressin receptor antagonists ( VRA ) . METHODS AND RESULTS Eligible patients had HF ( New York Heart Association Class II-III ) , systolic dysfunction ( left ventricular ejection fraction ≤0.40 ) and signs of congestion ( eg , edema , rales ) . At screening , patients were removed from baseline  diuretic therapy  and placed on a  low-sodium diet ( 2 g/day ) . After a 2-day run-in period , 83 patients were r and omized to placebo ( n = 21 ) , monotherapy with the vasopressin V2 receptor antagonist tolvaptan ( TLV ) 30 mg ( n = 20 ) , monotherapy with furosemide 80 mg ( FURO , n = 22 ) or both TLV 30 mg and FURO 80 mg ( n = 20 ) once daily for 7 days . Patients were on st and ard background therapy and not fluid-restricted throughout the study . A decrease in body weight of -1.37 ± 1.61 , -0.54 ± 1.59 , and -1.13 ± 1.49 kg was observed versus baseline for TLV , FURO , and TLV+FURO , respectively , at day 8 . At the same point , the placebo group showed a body weight increase of + 0.72 ± 2.42 kg versus baseline ( P = .0006 for TLV versus placebo ) . Increases in urine volume from baseline were greater with TLV alone ( 2646 ± 1503 mL/24 hours ) than with FURO ( 894 ± 853 mL/24 hours , P < .001 ) , or PLC ( 423 ± 786 mL/24 hours , P < .001 ) , and similar to TLV+FURO ( 2585 ± 2119 mL/24 hours ) . An increase in serum sodium within the normal range was also observed in TLV-treated patients ( P < .02 versus placebo ; P < .01 versus FURO ) . No changes in serum potassium , other laboratory values , or blood pressure were observed . TLV therapy was well tolerated . CONCLUSIONS In patients with HF and signs of volume overload , TLV monotherapy without concomitant loop diuretic therapy reduced body weight when compared to placebo without adverse changes in serum electrolytes , during a sodium restricted diet while on background medications including angiotensin-converting enzyme inhibitors and β-blockers BACKGROUND In heart failure patients , diuretics cause renin-angiotensin-aldosterone system ( RAS ) activation , which may lead to increased morbidity and mortality despite short-term symptomatic improvement . AIM To determine changes in RAS activation and clinical correlates following furosemide withdrawal in elderly heart failure patients without left ventricular systolic dysfunction . METHODS AND RESULTS We performed clinical assessment s and laboratory determinations of aldosterone , plasma renin activity ( PRA ) , atrial natriuretic peptide ( ANP ) , norepinephrine , and endothelin in 29 heart failure patients [ aged 75.1+/-0.7 ( mean+/-S.E.M. ) years ] , before , 1 and 3 months after placebo-controlled furosemide withdrawal .  Recurrent congestion occurred in 2 of 19 patients withdrawn , and in 1 of 10 patients continuing on furosemide . Three months after withdrawal , PRA had decreased -1.61+/-0.71 nmol/l/h ( P<0.05 ) . Decreases in aldosterone levels did not reach significance ( -0.17+/-0.38 nmol/l ) . The decreases in PRA after withdrawal correlated with decreases in systolic ( r(s)=0.61 , P=0.020 ) and diastolic blood pressure ( r(s)=0.80 , P=0.01 ) . Successful withdrawal was associated with increases in norepinephrine ( + 0.58+/-0.22 nmol/l ) and ANP ( + 3.5+/-1.3 pmol/l ) ( P<0.05 ) after 1 month , but these changes did not persist after 3 months . Endothelin levels did not change in both groups . CONCLUSION Successful furosemide withdrawal in elderly heart failure patients causes persistent decreases in RAS activation Seventeen patients with mild to moderate essential hypertension and controlled with antihypertensive drugs were treated with xipamid ( 40 mg ) or hydrochlorothiazide ( 50 mg ) in a double-blind cross-over r and omized trial design . After a run-in-period of 2 weeks with placebo , all of them received either of the two drugs . Placebo treatment for 2 weeks decreased both supine as well as st and ing blood pressure , but it was not statistically significant . Xipamid produced a somewhat greater decrease in blood pressure than hydrochlorothiazide , but the difference was not statistically significant . Similar results were obtained in 12 newly diagnosed cases of mild to moderate essential hypertension treated with xipamid ( 80 mg ) or hydrochlorothiazide ( 100 mg ) daily as single drug treatment in a r and omized , double-blind parallel design trial . The side effects produced by both drugs were only mild in nature . No significant changes were produced in serum electrolytes , uric acid and fasting blood glucose in this short term study with either of the drugs In a r and omized double-blind trial we compared the effects of torasemide , a new loop diuretic , and furosemide in nonazotemic cirrhotic patients with ascites during a 3-day period in association with potassium canrenoate ( 200 mg/day ) administration . Doses of loop diuretics administered in this trial ( 10 and 25 mg/day of torasemide and furosemide , respectively ) had been shown to be equipotent in healthy subjects .  Torasemide induced significantly greater natriuresis than furosemide ( p less than 0.02 ) , with a twofold greater percentage increase in basal values ( day 1 : 130 % vs. 50 % ; day 2 : 104 % vs. 42 % ; and day 3 : 65 % vs. 26 % , respectively ) . Body weight loss was significantly higher during torasemide ( p less than 0.02 ) administration , and the overall decrease at the end of the treatment was twice as high for furosemide ( 2.5 + /- 0.6 kg vs. 1.3 + /- 0.4 kg , respectively ) . Diuresis was also higher during torasemide administration , but the difference was not significant ( p = 0.08 ) . The extent of kaliuresis observed during the two treatments was almost identical despite the striking differences in the natriuretic response . The effects of the two treatments on plasma electrolytes , creatinine clearance , blood urea nitrogen , mean arterial pressure , heart rate and plasma arginine vasopressin concentration were similar . Both drugs caused increases in plasma renin activity at the end of the treatment , whereas plasma aldosterone concentration slightly increased only after torasemide administration . Despite the presence of a trend toward a more pronounced effect on these parameters after torasemide administration , no significant difference between the two treatments was observed . ( ABSTRACT TRUNCATED AT 250 WORDS Sixteen patients with moderate essential hypertension completed a double-blind crossover trial with four treatment periods each of 6 weeks . They received in r and om order : placebo ; tienilic acid 250 mg/day ; propranolol 80 mg twice daily ; and tienilic acid 250 mg/day combined with propranolol 80 mg twice daily . Average blood-pressure in the lying position was 22.6/13.1 kPa ( 169/98 mm Hg ) on placebo ; 21.0/12.5 ( 157/94 ) on tienilic aicd ; 21.2/12.0 ( 159/90 ) on propranolol , and 18.9/11.5 ( 142/86 ) on tienilic acid combined with propranolol . The effects of tienilic acid and propranolol on blood-pressure were additive and there were no statistically significant interactions . Tienilic acid significantly reduced serum-urate from 0.33 to 0.18 mmol/l and induced hypokalaemia which was corrected by propranolol .  Basophil count and haemoglobin were lower after tienilic acid treatment than they had been at the start of the study Sixteen patients with moderately severe essential hypertension completed a double-blind crossover trial with four treatment periods each lasting for six weeks . They received in r and om order , placebo ; tienilic acid 250 mg/day ; propranolol 80 mg b.d . ; and tienilic acid 250 mg/day and propranolol 80 mg b.d . in combination . Mean blood pressure in the lying position was 169/98 mmHg on placebo , 157/94 mmHg on tienilic acid , 159/90 mmHg on propranolol and 142/86 mmHg on the combination of tienilic acid and propranolol . The effects of tienilic acid and propranolol on blood pressure were additive and there was no evidence of any interaction . The onset of the hypotensive effect of tienilic acid was gradual while the effect of propranolol was maximal within 2 weeks of the start of treatment . Tienilic acid produced a significant reduction in serum urate from 0.33 mmol/l to 0.18 mmol/l . The combination of tienilic acid and propranolol in the doses used in the trial was effective and acceptable in the reduction of raised blood pressure BACKGROUND Acute decreases in intravascular volume are associated with increases in lipid levels . Furosemide causes acute changes in intravascular volume during prolonged therapy but is thought to have little effect on lipid levels . METHODS To determine if there are daily acute rises in lipid and lipoprotein levels associated with changes in intravascular volume during long-term furosemide ingestion therapy , we performed a r and omized , double-blind , placebo-controlled crossover study in 10 patients . RESULTS In the 8 hours after furosemide ingestion there were increases in levels of plasma cholesterol ( 10.1 % ; P = .001 ) , high-density lipoprotein cholesterol ( 9.0 % ; P = .006 ) , and apolipoprotein B ( 9.8 % ; P = .003 ) . The increases in levels of triglycerides ( 11.5 % ; P = .17 ) and apolipoprotein A-1 ( 13.3 % ; P = .051 ) were of similar magnitude but more variable and did not achieve statistical significance . There was no substantial change in the total cholesterol-high-density lipoprotein cholesterol ratio ( 0.6 % ; 95 % CI,-0.74 % to 8.6 % ; P = .88 ) . CONCLUSION This study indicates that there are acute increases in lipid levels after furosemide ingestion during prolonged therapy , which could affect the interpretation of lipid levels and cardiovascular risk in patients Previous studies in white and mixed-race hypertensive patient population s have generally found patients with low renin activity more responsive to diuretic therapy than patients with normal renin activity . Twenty-nine black patients ( 26 women and three men ) with placebo diastolic blood pressure of 90 to 115 mm Hg were treated with spironolactone ( 100 to 400 mg/day ) and hydrochlorothiazide ( 100/mg/day ) . Renin status was categorized by ( 1 ) the intravenous furosemide test , ( 2 ) ambulation during  placebo , and ( 3 ) ambulation during spironolactone and hydrochlorothiazide treatment . Only seven patients were categorized identically with all methods . No method identified a low renin subgroup that was more responsive to either spironolactone or hydrochlorothiazide .  Diastolic blood pressure fall with hydrochlorothiazide ( 18 mm Hg ) and 400 mg/day of spironolactone ( 15 mm Hg ) was similar . Thus , since black women with both low and normal renin activity are quite responsive to diuretics , renin classification to guide initial antihypertensive selection is not warranted The enantiomers of indacrinone ( I ) , an investigational loop diuretic , have different pharmacologic activity . The ( - ) enantiomer is natriuretic , and the ( + ) enantiomer is uricosuric . To determine the antihypertensive effects and an isouricemic ratio of indacrinone enantiomers , 37 patients with sitting diastolic blood pressure ( BP ) between 90 and 104 mm Hg , after a 4-week placebo washout , r and omly received one of the ratios of I enantiomers , namely -2.5/+80 mg ( A ) , -5/+80 mg ( B ) , -10/+80 mg ( C ) or placebo ( P ) , once daily for 12 weeks in a double-blind , parallel study . The mean reductions ( baseline-end of treatment ) in BP of 23/8 , 20/10 and 25/10 mm Hg with treatments A , B and C respectively were greater ( p less than 0.01 ) than that on P ( 0/3 ) . Initially , serum uric acid decreased with treatments A and B but not with C. Mean changes in serum uric acid were -0.3 , -0.4 , 0.2 and 0.3 mg/dl respectively with treatments A , B , C and P. The ratio of -10/+80 mg produced least variation in serum uric acid . Reduction in serum K+ and Cl- appeared to be dose related to ( - ) enantiomer . No serious adverse effects were reported . A 1:9 ratio of I enantiomers intended for wide-scale use as a diuretic also showed good antihypertensive activity , a favorable uric acid profile and absence of hepatic toxicity in 14 patients In a r and omized double-blind parallel group study conducted in three centres the hypotensive activity of piretanide 6 mg b.i.d . was compared with that of hydrochlorothiazide ( HCT ) 25 mg b.i.d . and HCT 50 mg b.i.d . Ninety-three patients entered the study and sixty-one completed a 16–week trial period . All three treatments produced a significant reduction in supine diastolic and systolic blood pressure after only 2 weeks of active treatment and this was maintained for the duration of the study . The mean maximal reduction in supine diastolic blood pressure was 18 % in the piretanide group , 18·8 % in the HCT 25 mg b.i.d . group , and 20 % in the HCT 50 mg b.i.d . group . The corresponding figures for the percentage of patients attaining a supine diastolic pressure below 95 mm Hg were 83 % , 62 % and 89 % . There were no significant differences between the three groups . Side-effects were generally mild and transient , except for polyuria which was noted in all three groups but more commonly in the piretanide group . Two patients were withdrawn because of side-effects : one patient in the high dose HCT group developed severe postural symptoms ; and one patient in the low dose HCT group was withdrawn because of restlessness , nausea , weakness , dizziness and somnolence . All three treatments caused a significant increase in serum uric acid concentrations . Four patients in each of the HCT groups developed hypokalemia , but no patients in the piretanide group did so The antihypertensive action of furosemide was evaluated in double-blind studies conducted in three different hospital clinics , by investigators following an identical protocol . The pressure lowering effect of furosemide was compared with that of a placebo in a r and omized cross-over study . Both systolic and diastolic pressures were lowered significantly from pretreatment levels in over 50 % of patients . No clinical ly important side effects attributable to furosemide were encountered in this study . Hyperuricemia was encountered in 31 of 44 patients . No significant disturbances of electrolyte balance were noted . Statistical analysis of the pooled data supported the conclusion that furosemide exerts an antihypertensive effect similar to that of other widely used sulfonamide diuretics , and therefore appears to be an effective agent for the treatment of mild to moderate hypertension Efficacy and tolerance of cicletanine , the first derivative of furopyridines have been studied in a 3 parallel groups double blind study ; 120 essential mild hypertensive patients uncontrolled by beta blocking therapy were included . After a period of one month during which a treatment by placebo was added to beta blocking therapy , the patients were r and omly allocated into 3 groups : group I ( placebo : 40 patients ) , group II ( cicletanine 50 mg/d : 41 patients ) , group III ( cicletanine 100 mg/d : 39 patients ) . Eight patients were withdrawn in the group I ( poor efficacy , n = 5 or unexpected event , n = 3 ) , and one in the group III ( unexpected event ) . At the beginning of the treatment period ( DO ) , lying blood pressure ( LBP ) was respectively for groups I , II and III 171 + /- 14/104 + /- 6 , 174 + /- 13/104 + /- 5 , 172 + /- 15/105 + /- 6 mmHg . 171 + /- 14/104 + /- 6 , 174 + /- 13/104 + /- 5 , 172 + /- 15/105 + /- 6 mmHg . After 3 months of treatment LBP was respectively 168 + /- 21/97 + /- 10 , 151 + /- 12/85 + /- 7 , 147 + /- 14/82 + /- 9 mmHg . A significant treatment effect ( p less than 0.001 ) was observed on SBP with groups II and III only , and on DBP with the 3 groups . This lowering effect was comparable in groups II and III , and greater ( p less than 0.001 ) in these groups than in group I. At the end of this study the percentage of patients whose BP was normalized was respectively for groups I , II and III : 5 p. 100 , 51 p. 100 and 74 p. 100 . Clinical and biological tolerance were good . ( ABSTRACT TRUNCATED AT 250 WORDS Out of thirty-six patients with mild to moderate hypertension twenty-six patients completed a double-blind comparison of slow-release frusemide at two dose levels , and placebo . The two groups differed in their age pattern , baseline level of blood pressure and response to a low-salt diet during the wash-out/run-in period . Despite the lack of comparability of the two groups , firm clinical inferences could be drawn from the study . Seven of the eighteen placebo  patients had to be withdrawn from further participation because of deterioration in their hypertension : in contrast , fifteen of the eighteen frusemide patients showed an anti-hypertensive response and none was withdrawn because of lack of effect . Twice-daily administration of the slow-release formulation , however , produced an unacceptable level of such side-effects as nocturia , nausea and vomiting . Once-daily administration of the preparation is therefore preferred A double-blind crossover study was carried out in 20 patients with mild to moderate essential hypertension to assess the efficacy and tolerability of a low fixed-dose combination containing 20 mg penbutolol ( a beta-blocking agent ) and 3 mg piretanide ( a diuretic ) in comparison to placebo over a period of 4 weeks . Active drug treatment in the 20 patients studied was preceded by a 1-week period of placebo . The results showed that there was an effective significant reduction in systolic and diastolic blood pressure compared with initial levels in the fixed-dose combination group , when compared to the placebo group , both at rest , during maximal ergometric and isometric work load , and also in the diurnal blood pressure profile over 24 hours . Pulse rate also decreased in the combination group . The biochemical , haematological and urinary parameters showed no clinical ly relevant changes in either group during the entire study period . Minor side-effects definitely or probably associated with the treatment were observed in both groups but were generally mild and did not interfere with treatment . No patient withdrew prematurely from the trial Nineteen patients with pre-eclampsia were r and omised to receive 40 mg of frusemide or placebo by mouth daily for 7 days in the first post-partum week . Outcome measures included mean and maximum blood pressure , the need for additional antihypertensive treatment during that period and mean length of hospital stay . There were no statistically significant differences in outcome between the treatment and placebo groups although there was a trend to more rapid lowering of blood pressure following delivery in those receiving frusemide AIMS Diuretics , when used to treat congestion in patients with chronic heart failure , improve symptoms and , perhaps , prognosis but little information is available to guide their use in patients with left ventricular systolic dysfunction ( LVSD ) who are not congested . Chronic diuretic therapy causes persistent and potentially harmful neuroendocrine activation . Alternatively , in patients in whom neuroendocrine activation is blocked with angiotensin-converting enzyme (ACE)-inhibitors and beta-blockers , diuretics may be beneficial by decreasing preload and afterload and preventing congestion . We aim ed to assess the effect of the loop diuretic , torasemide on quality of life , and surrogate markers of prognosis when given to patients with LVSD who were not clinical ly congested and who were optimally treated with ACE-inhibitors ( or angiotensin receptor antagonists ) and beta-blockers . METHODS AND RESULTS Thirty patients with stable LVSD who had no clinical ly detectable fluid overload were r and omized to receive either torasemide 5 mg daily or placebo for 3 months ( Phase A ) , and after a washout phase of 2 months , cross-over was performed for 3 months ( Phase B ) . Diuretic therapy did not cause significant change in peak VO(2 ) , mean N-terminal pro-hormone brain natriuretic peptide ( NT-proBNP ) levels , or measures of quality of life compared with placebo . Diuretic therapy did however lead to significant fall in systolic and diastolic blood pressures and increase in plasma renin levels compared with placebo . CONCLUSION Diuretic therapy with torasemide is not superior to placebo in improving peak VO(2 ) or reducing NT-proBNP levels in patients with left ventricular dysfunction who are not clinical ly congested The effectiveness of a new potent diuretic , xipamide , was evaluated in the treatment of patients with mild to moderate essential hypertension . The effects of daily doses of 40 mg xipamide were compared with those of 100 mg chlorthalidone with respect to systolic and diastolic blood pressure , using a double-blind crossover design . Patients received each drug for 6 weeks , the order of treatments being at r and om and the periods being separated by a ' washout ' period of 7 days . The results showed that xipamide was as effective as chlorthalidone in controlling blood pressure , both in the upright and supine positions , and when administered after chlorthalidone produced a further reduction . No such further reduction occurred when chlorthalidone was given after xipamide . Serum electrolyte changes induced by the two diuretics were comparable . Both drugs were well tolerated and caused few side-effects To test the hypothesis that alternate-day administration of furosemide will result in a sustained improvement in pulmonary function without causing alterations in electrolyte or mineral homeostasis , we conducted a r and omized , double-blind , placebo-controlled study of 11 hospitalized , oxygen-dependent , spontaneously breathing infants with chronic bronchopulmonary dysplasia . Infants were r and omly selected to receive either furosemide , 4 mg/kg in two divided doses on alternate days orally , or placebo for 8 days , followed by crossover to the alternate-therapy for an additional 8-day period . The two study periods were separated by a 48-hour washout period . Dynamic compliance , total pulmonary resistance , the concentration of electrolytes in serum , and the concentrations of calcium and creatinine in urine were measured on nontreatment days . Alternate-day furosemide therapy increased dynamic lung compliance by 76 + /- 112 % and decreased total pulmonary resistance by 20 + /- 39 % , compared with placebo ( both variables p = 0.032 ) . Alternate-day furosemide therapy did not result in increased urine output , electrolyte abnormalities , or increased urinary calcium excretion . We conclude that this simplified treatment regimen may be useful in the management of infants with chronic bronchopulmonary dysplasia . The results support our previous speculation that furosemide improves pulmonary function by mechanisms unrelated to its diuretic properties To test the dose responses of piretanide , ramipril , and their combination in patients with essential hypertension , a prospect i ve , r and omized , double-blind , placebo-controlled trial was conducted in 480 patients . Twelve separate groups were studied : placebo , piretanide 3 mg , piretanide 6 mg , ramipril 2.5 mg , ramipril 5 mg , ramipril 10 mg , and their combinations , as single daily morning doses . Patients were r and omized after a 2-week run-in period without drugs ; treatment was given for 6 weeks . A dose response compared with placebo was found for both drugs ; the combination was more effective than either drug alone . Piretanide 6 mg , combined with ramipril 5 mg , provided optimal blood pressure reduction . Self-reported adverse effects of both drugs and their combinations did not exceed those reported for placebo . A surface analysis suggested that piretanide primarily reduced systolic blood pressure , whereas ramipril was more effective in reducing diastolic blood pressure . The data attest to a combined efficacy of piretanide and ramipril in decreasing arterial blood pressure A double-blind , r and omized , crossover trial was carried out in 26 hypertensive patients to investigate the hypotensive effects of three different dosages of frusemide ( 40 mg , 60 mg , and 80 mg twice daily ) and the effects on serum potassium and urinary output . The study included a 4-week treatment period with placebo , three periods of 6 weeks with frusemide , and an intervening placebo period of 4 weeks . The mean arterial blood pressure fell about 10 mmHg within the first 2 weeks and was independent of the frusemide dosage . During the following weeks of treatment , there was a constant , slow fall in blood pressure . The period on placebo was too brief for values to return to the initial level . In contrast , the increase in urinary output , which was dose-dependent , ceased when medication was withdrawn . The diuretic effect was maintained throughout the treatment periods . There was a correlation between the fall in serum potassium and the diuretic effect whereas no correlation with the fall in blood pressure could be shown . Except for a significant increase in serum zinc , no changes were observed in other electrolyte parameters . Body weight , pulse , haemoglobin and erythrocyte sedimentation rate remained unchanged . Side-effects were few and mild , but tended to increase with higher doses 1 . We have determined the ventilatory response to CO 2 at two levels of end-tidal O 2 tension in eight normal subjects before and after ( 1 ) 4 days of 0.242 mmol ( 80 mg ) oral frusemide daily and ( 2 ) 4 days of 0.024 mmol ( 10 mg ) bendrofluazide daily . 2 . Frusemide produced no significant alkalosis , change in end-tidal CO 2 tension or alteration in the CO 2 response line . However , we did demonstrate a linear relationship between the change in plasma total CO 2 content and the change in intercept of the CO 2 response line in hyperoxia after frusemide . 3 . Bendrofluazide produced a metabolic alkalosis with no significant change in end-tidal CO 2 tension . The CO 2 response line after the drug showed a decrease in slope in hyperoxia and a shift to the right of the intercept in hypoxia . There was no relationship between change in plasma total CO 2 content and change in the intercept of the CO 2 response line in hyperoxia . 4 . If these results obtained on normal subjects are applicable to patients with chronic bronchitis and emphysema , frusemide might be the diuretic of choice for use with controlled oxygen therapy in the management of acute exacerbations of this disease when it is complicated by ventilatory failure In a double-blind study , thirty patients having mild to moderate essential hypertension were r and omly assigned to a six week regimen of either tienilic acid , hydrochlorothiazide , or placebo .  Blood pressure was significantly reduced with tienilic acid and hydrochlorothiazide although more so with tienilic acid .  Serum uric acid declined strikingly with tienilic acid and increased significantly with hydrochlorothiazide .  Serum potassium declined slightly with tienilic acid but more so with hydrochlorothiazide .  Serum creatinine and blood urea nitrogen increased slightly more with tienilic acid than with hydrochlorothiazide . There were no clinical adverse effects to any of the medications during this study . Twenty-four months of continuous administration of tienilic acid revealed maintenance of blood pressure effect , but with slight increases in blood urea nitrogen , serum creatinine and uric acid and slight decreases in serum potassium as compared to six weeks administration . Tienilic acid appears to be a useful new antihypertensive agent . The hypouricaemic effect is profound and strongly suggests the need for continuing evaluation of this compound because of its unique combination of diuretic , antihypertensive and hypouricaemic properties 本態性高血圧に対する利尿降圧剤 tripamide 1日15～60mg単独投与の有用性を60歳以上の老年者33例 ( 平均年齢65.9歳 ) と59歳以下の壮年者59例 ( 平均年齢50.0歳 ) に於て二重盲検法により検討した.降圧効果 ( 20/10mmHgまたは平均血圧13mmHg以上下降 ) は老年者で84.8 % , 壮年者で59.3%で , 老年者の降圧効果が有意に高いことを認めた ( p<0.05 ) . しかし降圧幅は老年者で32.0/13.2mmHg , 壮年者で26.9/11.2mmHgであり , 有意差を認めず , 老年者で過度の降圧を来さないことを示唆した.臨床検査のうち , 血液学検査では両年齢群とも有意の変動を認めず , 血液濃縮は見られなかった. 生化学検査では老年者では血清Cl , アルカリフォスファターゼの低下と尿素窒素 , 尿酸の上昇を , 壮年者では血清Clの低下と総コレステロール , Ca , 尿酸 , 尿素窒素の上昇を認めた. 血清Na , K , 空腹時血糖値には両年齢群とも変化を認めなかった. 心胸比は老年者で減少した. これらの変化は有意差を認めたものの正常範囲内の変化であり臨床的意義は少ないと思われる.副作用は壮年者で5例8%に認められたが , 老年者では認められなかった. 副作用に臨床検査値の異常変化例を含めると壮年者で9例15 % , 老年者で4例12%でいずれも有意差は見られなかった.従って有用性 ( 有用以上 ) は , 老年者で78.8 % , 壮年者で52.5%と有意差を認め ( p<0.05 ) , 利尿降圧剤 tripamide Angiotensin is a potent coronary vasoconstrictor , but little is known of the effects of long-term activation of the renin-angiotensin system on coronary reserve in humans . The effects of exercise on coronary hemodynamics were determined in eight patients with mild essential uncomplicated hypertension , before and after treatment with furosemide ( 50 mg , to ensure activation of the renin-angiotensin system ) . Coronary sinus blood flow was measured by thermodilution technique , intra-arterial blood pressure was measured from the ascending aorta , and plasma renin activity was determined by radioimmunoassay . Oxygen supply and dem and were derived ( using coronary sinus blood flow multiplied by the arteriovenous oxygen difference to equal oxygen supply and heart rate multiplied by the mean systolic blood pressure to equal oxygen dem and ) both at rest and during isometric exercise ( h and grip to 50 percent of maximal effort for three minutes ) . The study was a single-blind crossover ( furosemide versus placebo ) design . Furosemide produced a significant reduction in coronary sinus blood flow , associated with an increase in coronary vascular resistance . Changes in mean arterial pressure and heart rate were insignificant . Slight reductions in plasma volume and mean right atrial pressure were observed . During isometric exercise , the increase in oxygen supply for a given increment in oxygen dem and was attenuated by furosemide . The contribution of the renin-angiotensin system to this effect was determined by the short-term administration of 25 mg of the angiotensin converting enzyme inhibitor captopril . Forty-five minutes after oral captopril , coronary reserve was restored to pretreatment values . In conclusion , furosemide modulates coronary reserve , and it is likely that this is because furosemide mediates activation of renin-angiotensin system , thus reducing the vasodilatory capacity of the coronary arteries
target: We found no clinical ly meaningful blood pressure-lowering differences between different drugs within the loop diuretic class .
background: BACKGROUND Antihypertensive drugs from the thiazide diuretic drug class have been shown to reduce mortality and cardiovascular morbidity .
  Loop diuretics are indicated and used to treat hypertension , but a systematic review of their blood pressure-lowering efficacy or effectiveness in terms of reducing cardiovascular mortality or morbidity from r and omized controlled trial ( RCT ) evidence has not been conducted .
  OBJECTIVES To determine the dose-related decrease in systolic or diastolic blood pressure , or both , as well as adverse events leading to participant withdrawal and adverse biochemical effects ( serum potassium , uric acid , creatinine , glucose and lipids profile ) due to loop diuretics versus placebo control in the treatment of people with primary hypertension .