Converting-enzyme inhibition buffers the counter-regulatory response to acute administration of nicardipine.
1. To investigate the interaction of angiotensin-converting-enzyme (ACE) inhibitor and calcium antagonist, we conducted a double-blind randomized, placebo-controlled crossover study of a new ACE inhibitor (CGS 14824 A, 20 mg) during intravenous administration (i.v.) of nicardipine in eight normotensive healthy subjects. Nicardipine was infused to give cumulative doses of 1.25, 3.75, and 8.75 mg after 10, 20 and 30 min. 2. ACE inhibition was demonstrated 24 h after the first CGS 14 824 A intake (61%). Three hours after the second dose this inhibition was more marked (98%). 3. I.v. nicardipine administration induced a significant and similar fall in systolic or diastolic blood pressure with and without ACE activity (-3/-6 vs -2/-8%), while tachycardia was significantly decreased by CGS 14 824 A (+14 vs +30%, P less than 0.02). The increase of plasma noradrenaline was also significantly blunted (+1.8 +/- 0.3 vs +3.1 +/- 0.7 pmol ml-1, P less than 0.05). 4. Active and total plasma renin increased at the end of nicardipine infusion in the presence or absence of ACE inhibition. Inactive renin did not increase after nicardipine infusion under placebo. It was higher 3 h after the second intake of CGS 14 824 A and then increased after nicardipine infusion. 5. The rise in plasma aldosterone during i.v. calcium antagonist infusion was diminished after ACE inhibition (126 +/- 39 vs 277 +/- 120 pmol l-1, P less than 0.02). 6. In conclusion, converting-enzyme inhibition buffers the rise in heart rate, plasma noradrenaline and plasma aldosterone induced by acute calcium blockade.
Bellet
M
M
Service d'hypertenion Arterielle, Hôpital Broussais, Paris, France.
Sassano
P
P
Guyenne
T
T
Corvol
P
P
Menard
J
J
D000328:Adult; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D001552:Benzazepines / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects; D002395:Catecholamines / Q000097:blood; D004311:Double-Blind Method; D004347:Drug Interactions; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D008297:Male; D009529:Nicardipine / Q000494:pharmacology*; D011897:Random Allocation; D012084:Renin-Angiotensin System / Q000187:drug effects
D000806:Angiotensin-Converting Enzyme Inhibitors; D001552:Benzazepines; D002395:Catecholamines; D009529:Nicardipine; C044946:benazepril