8540
document
Effects of enalapril and eprosartan on the renal vascular nitric oxide system in human essential hypertension . BACKGROUND Experimental data in humans on the contribution of angiotensin-converting enzyme inhibitors and angiotensin II type 1 receptor blockers to the nitric oxide system of the renal vasculature are inconsistent . Enalapril and eprosartan , alone and in combination , were used to determine their short-term effects on the renal nitric oxide system and renal hemodynamics of human subjects with essential hypertension . METHODS Twenty male , white patients ( 27 +/- 1 years ) with mild essential hypertension ( 143 +/- 11/95 +/- 6 mm Hg ) were included in a double-blind , randomized , placebo-controlled , fourfold cross-over study with placebo , enalapril ( 20 mg/day ) , eprosartan ( 600 mg/day ) , or combination of both drugs ( 10 and 300 mg/day , respectively ) each over a one week period followed by a two-week washout phase . After each study phase the glomerular filtration rate ( GFR ) and renal plasma flow ( RPF ) were determined . Basal nitric oxide synthesis of the renal vasculature was assessed by the decrease in RPF after inhibition of nitric oxide synthase with NG-monomethyl-L-arginine ( L-NMMA ; 4.25 mg/kg ) . RESULTS After one week of therapy , the combination therapy decreased casual blood pressure by 5 +/- 2/3 +/- 1 mm Hg versus placebo ( P < 0.01 ) . Neither enalapril alone ( -2 +/- 2/1 +/- 2 mm Hg , NS vs. placebo ) nor eprosartan alone ( -1 +/- 1/0 +/- 2 mm Hg , NS vs. placebo ) had a clear-cut significant effect on casual blood pressure . In the combination phase , RPF increased by 123 +/- 36 mL/min ( P < 0.01 ) . Neither enalapril alone ( +59 +/- 46 mL/min , P = 0.21 ) nor eprosartan alone ( +113 +/- 51 mL/min , P = 0.06 ) had a clear-cut significant effect on RPF . Changes of RPF induced by treatment correlated with the L-NMMA induced decrease in RPF in the combination ( r = 0.70 , P < 0.01 ) and eprosartan phase ( r = 0.86 , P < 0.001 ) , but not in the enalapril phase ( r = -0.44 , P = 0.10 ) . Renal vascular resistance was reduced by each active treatment with the most prominent reduction in the combination phase . GFR was unaffected by any treatment . CONCLUSIONS In contrast to the effects of either substance alone , a combination of half the dose of eprosartan with half the dose of enalapril had a prominent effect on renal perfusion . The effects of eprosartan on RPF are mediated , at least in part , by an increased bioavailability of nitric oxide in the renal vasculature .
8541
Intervention_Pharmacological
enalapril
8542
Intervention_Pharmacological
eprosartan
8543
Intervention_Pharmacological
Enalapril
8544
Intervention_Pharmacological
eprosartan
8545
Intervention_Control
placebo-controlled
8546
Intervention_Control
placebo
8547
Intervention_Pharmacological
enalapril ( 20 mg/day )
8548
Intervention_Pharmacological
eprosartan ( 600 mg/day )
8549
Intervention_Pharmacological
combination of both drugs
8550
Intervention_Pharmacological
combination therapy
8551
Intervention_Pharmacological
enalapril
8552
Intervention_Pharmacological
eprosartan
8553
Intervention_Pharmacological
eprosartan
8554
Intervention_Pharmacological
enalapril
8555
Intervention_Pharmacological
eprosartan
8556
Outcome_Other
effects
8557
Outcome_Physical
glomerular filtration rate ( GFR ) and renal plasma flow ( RPF )
8558
Outcome_Physical
renal vasculature
8559
Outcome_Physical
RPF
8560
Outcome_Physical
casual blood pressure
8561
Outcome_Physical
casual blood pressure
8562
Outcome_Physical
RPF
8563
Outcome_Physical
RPF
8564
Outcome_Physical
RPF
8565
Outcome_Physical
Renal vascular resistance
8566
Outcome_Physical
GFR
8567
Outcome_Physical
renal perfusion
8568
Outcome_Other
bioavailability of nitric oxide
8569
Participant_Condition
human essential hypertension .
8570
Participant_Condition
human subjects with essential hypertension .