Additive effects of losartan and enalapril on blood pressure and plasma active renin

The combination of single oral doses of an angiotensin I-converting enzyme inhibitor (captopril) and a type 1 angiotensin II receptor antagonist (losartan) has additive effects on blood pressure fall and renin release in sodium-depleted normotensive subjects. We planned the present study to determine whether the magnitude of the hemodynamic and hormonal consequences of renin-angiotensin system blockade by such a combination is larger than that obtained by doubling the dose of the angiotensin-converting enzyme inhibitor given alone. In a single-dose, double-blind, randomized, three-way crossover study, 10 mg enalapril, 20 mg enalapril, and the combination of 50 mg losartan and 10 mg enalapril were administered orally to 12 sodium-depleted normotensive subjects. The area under the time curve from 0 to 24 hours (AUC(0-24)) of the mean blood pressure fall after losartan-enalapril combination intake (-220+/-91 mm Hg . h) was significantly greater than that of either 10 or 20 mg enalapril (-124+/-91 and -149+/-85 mm Hg . h, respectively; P<.05 vs both doses). The combination significantly increased by 2.3+/-1.2-fold the AUC(0.24) of plasma active renin compared with either 10 or 20 mg enalapril given alone (P<.05) but had no additive effect on plasma aldosterone fall. The losartan-enalapril combination is more effective in decreasing blood pressure and increasing plasma active renin than doubling of the enalapril dose.