Hemodynamic and Humoral Responses to Enalapril and Nifedipine in the Rat

Abstract

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 twofold. 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.

Key Words:

• Angiotensin converting enzyme
• calcium
• antagonists
• rennin
• spontaneously hypertensive rat
• hypertension