Hemodynamic and humoral responses to enalapril and nifedipine in the rat.
The hemodynamic and humoral effects of enalapril, an angiotensin converting enzyme (ACE) inhibitor, and nifedipine, a calcium-entry blocker, were evaluated in conscious spontaneously hypertensive rats (SHR). Rats received enalapril (5 mg/kg, po) or vehicle, followed in one hour by nifedipine (2.5 mg/kg, ip) or its vehicle. After treatment with enalapril alone, systolic blood pressure (BP) declined over a 3 hour period from 204 +/- 4 (mean +/- SE) to 168 +/- 6 mm Hg and remained suppressed for an additional 4 hours. Heart rate (HR) did not change. Plasma renin activity (PRA) increased approximately 9-fold and serum ACE was maximally inhibited. BP response to nifedipine was more rapid, greater in magnitude (-59 +/- 6 mm Hg) and shorter in duration; heart rate increased and remained elevated for 2.5 hours. PRA only rose two-fold. After the drugs in combination, BP declined as rapidly and to the same degree as after nifedipine and remained reduced for a longer duration. Treatment with enalapril attenuated the reflex tachycardia observed after nifedipine. These data suggest that coadministration of an ACE inhibitor and calcium-entry blocker may provide better blood pressure control than either drug class alone and at the same time prevent the reflex tachycardia frequently observed after nifedipine.
D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects*; D004151:Dipeptides / Q000494:pharmacology*; D004656:Enalapril; D006339:Heart Rate / Q000187:drug effects*; D007700:Kinetics; D008297:Male; D009543:Nifedipine / Q000494:pharmacology*; D051381:Rats; D011918:Rats, Inbred SHR; D012084:Renin-Angiotensin System / Q000187:drug effects
D000959:Antihypertensive Agents; D004151:Dipeptides; D004656:Enalapril; D009543:Nifedipine