COMPARISON OF CALCIUM-CHANNEL INHIBITORS ON VAGAL HEART-RATE RESPONSES ELICITED BY ARTERIAL BARORECEPTOR REFLEXES IN ANESTHETIZED DOGS

  • 1 January 1984
    • journal article
    • research article
    • Vol. 228  (2) , 491-499
Abstract
Actions of the Ca 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 .mu.g/kg per min i.v.) and diltiazem (3.0-30 .mu.g/kg per min i.v.) at 20 min after starting each dose and by verapamil (100 .mu.g/kg i.v. loading dose plus 1.0-30 .mu.g/kg per min i.v.) at 10 min after each dose. Nifedipine (0.1-3.0 .mu.g/kg per min i.v. at 20 min) and sodium nitroprusside (3.0-20 .mu.g/kg per 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. Nimodipine (0.3 and 1.0 .mu.g/kg per 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. The composite tachycardiac responses (i.e., tonic heart rate plus acetylcholine-induced reflex changes) were never reduced by any of the test agents. Some, but not all of the Ca channel inhibitors evidently interfered with activation of the baroreceptor-vagal reflex arc; however, none of the agents changed reflex responses caused by baroreceptor deactivation. For nimodipine, the site of action was confined to peripheral baroreceptor sensory elements. Differences in the effects of the 2 dihydrophyridine Ca channel inibitors, nimodipine and nifedipine, may prove useful for elucidating the mechanism of inhibitory action.

This publication has 21 references indexed in Scilit: