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 (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.
Azizi
M
M
Broussais Hospital Clinical Investigation Center, Institut National de la Santé et de la Recherche Médicale (INSERM), Paris, France.
Guyene
T T
TT
Chatellier
G
G
Wargon
M
M
Ménard
J
J
D000293:Adolescent; D000328:Adult; D000450:Aldosterone / Q000097:blood; D000803:Angiotensin I / Q000097:blood / Q000187:drug effects; D000804:Angiotensin II / Q000097:blood / Q000187:drug effects; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D000959:Antihypertensive Agents / Q000494:pharmacology*; D001713:Biphenyl Compounds / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects*; D018592:Cross-Over Studies; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004656:Enalapril / Q000494:pharmacology*; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D006854:Hydrocortisone / Q000097:blood; D007093:Imidazoles / Q000494:pharmacology*; D019808:Losartan; D008297:Male; D007703:Peptidyl-Dipeptidase A / Q000097:blood / Q000187:drug effects; D012083:Renin / Q000097:blood* / Q000187:drug effects; D013777:Tetrazoles / Q000494:pharmacology*; D013997:Time Factors
D000806:Angiotensin-Converting Enzyme Inhibitors; D000959:Antihypertensive Agents; D001713:Biphenyl Compounds; D007093:Imidazoles; D013777:Tetrazoles; D000804:Angiotensin II; D000450:Aldosterone; D004656:Enalapril; D000803:Angiotensin I; D007703:Peptidyl-Dipeptidase A; D012083:Renin; D019808:Losartan; D006854:Hydrocortisone