(Hypertension. 1997;29:634-640.)
© 1997 American Heart Association, Inc.
Articles |
Additive Effects of Losartan and Enalapril on Blood Pressure and Plasma Active Renin
the Broussais Hospital Clinical Investigation Center, Institut National de la Sante et de la Recherche Medicale (INSERM) et Assistance Publique des Hopitaux de Paris (M.A., T.-T.G., G.C., M.W., J.M.), and INSERM U 367 (J.M.), Paris, France.
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 (AUC0-24) 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 AUC0-24 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.
Key Words: blood pressure • angiotensin-converting enzyme inhibitors • angiotensin II • renin • sodium • drug synergism
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