Arterial and endocrine effects of a combination of an angiotensin converting enzyme inhibitor and a vasodilator in normotensive healthy volunteers.
The aim of the present study was to look for possible additive or synergistic effects of the combined oral administration of a single dose of an angiotensin converting enzyme (ACE) inhibitor, benazepril (10 mg) (B), and a long-acting vasodilator, cadralazine (5 mg) (C), on blood pressure, arterial parameters, and active plasma renin. The study was carried out in eight normotensive subjects according to a double-blind, randomized, placebo-controlled, crossover design. Blood pressure (BP), heart rate, humeral artery diameter (D), carotid-femoral pulse-wave velocity (PWV), finger-pulse ratio (FPR), and plasma active renin (PAR) were measured at baseline and every 2 h over 8 h. A significant treatment effect was observed for supine and tilted BP, FPR, PWV, and PAR. The largest decrease in supine systolic and diastolic BP was observed with the combination (10.0 +/- 6.9/7.2 +/- 3.7 mm Hg). Six hours after drug intake, the mean changes in FPR were 0.05 +/- 0.24 (P), -0.06 +/- 0.30 (C), 0.13 +/- 0.32 (B), and 0.28 +/- 0.34 (B + C), and the mean changes in PWV were 0.14 +/- 0.66 m/s (P), 0.09 +/- 0.54 m/s (C), -0.29 +/- 0.50 m/s (B), and -0.55 +/- 0.48 m/s (B + C). PAR was more markedly augmented with the combination of the two drugs (142 +/- 40 pg/ml) than with benazepril alone (90 +/- 62 pg/ml). It was concluded that a single noneffective dose of a vasodilator administered together with an ACE inhibitor in normotensives can lower blood pressure and increase arterial compliance and plasma active renin.
Brunel
P
P
Pharma Research and Development, CIBA-GEIGY Limited, Basel, Switzerland.
Guyene
T T
TT
Howald
H
H
Ménard
J
J
D000284:Administration, Oral; D000328:Adult; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D000959:Antihypertensive Agents / Q000494:pharmacology*; D001552:Benzazepines / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects*; D004311:Double-Blind Method; D004357:Drug Synergism; D006339:Heart Rate / Q000187:drug effects*; D006801:Humans; D008297:Male; D010865:Pilot Projects; D011187:Posture; D011724:Pyridazines / Q000494:pharmacology*; D011897:Random Allocation; D012083:Renin / Q000097:blood
D000806:Angiotensin-Converting Enzyme Inhibitors; D000959:Antihypertensive Agents; D001552:Benzazepines; D011724:Pyridazines; C031877:cadralazine; D012083:Renin; C044946:benazepril