Comparison of calcium channel inhibitors on vagal heart rate responses elicited by arterial baroreceptor reflexes in anesthetized dogs

DG Taylor and TE Kowalski

Actions of the calcium channel inhibitors, nimodipine, nifedipine, verapamil and diltiazem, and the direct-acting vasodilator, sodium nitroprusside, were compared on baroreceptor reflex-induced bradycardia elicited by pressor responses produced by norepinephrine and on reflex- induced tachycardia elicited by the hypotensive responses to acetylcholine in alpha-chloralose anesthetized dogs. Beta adrenoceptor blockade with propranolol was maintained throughout the experiments to assure that the cardiac reflexes were vagal in origin. The reflex vagal bradycardic ratio (-delta heart rate/+delta blood pressure) elicited by norepinephrine-induced pressor responses was reduced dose-dependently by nimodipine (0.1-1.0 micrograms/kg/min i.v.) and diltiazem (3.0-30 micrograms/kg/min i.v.) at 20 min after starting each dose and by verapamil (100 micrograms/kg i.v. loading dose plus 1.0-30 micrograms/kg/min i.v.) at 10 min after each dose. In contrast, nifedipine (0.1-3.0 micrograms/kg/min i.v. at 20 min) and sodium nitroprusside (3.0-20 micrograms/kg/min i.v. at 20 min) did not inhibit the bradycardic ratio. Resting mean arterial blood pressure was reduced similarly by all of the agents and tonic heart rate was essentially unchanged. Studies on the site of action revealed that nimodipine (0.3 and 1.0 micrograms/kg/min i.v. at 20 min) attenuated the reflex vagal bradycardia evoked by pressure elevations in the isolated carotid sinus, but did not change the reflex responses elicited by electrical stimulation of afferent fibers in the carotid sinus nerve. The reflex tachycardic ratio (+ delta heart rate/-delta blood pressure) evoked by acetylcholine-induced hypotensive responses was reduced in a dose- related fashion by all of the agents.(ABSTRACT TRUNCATED AT 250 WORDS)

Volume 228, Issue 2, pp. 491-499, 02/01/1984
Copyright © 1984 by American Society for Pharmacology and Experimental Therapeutics