Direct effects of diltiazem, nifedipine and verapamil on peripheral sympathetic nerve function, cardiac impulse conduction and cardiovascular function in anesthetized dogs subjected to ganglionic blockade.
The Ca2+ entry blockers diltiazem, nifedipine and verapamil produced dose-dependent increases in atrioventricular conduction time (A-H interval), while decreasing heart rate and mean arterial pressure in anesthetized dogs previously subjected to ganglionic blockade to prevent hypotension-induced reflex changes in sympathetic tone. Nifedipine and verapamil, but not diltiazem, also reduced (P less than 0.05) the tachycardia produced by electrical stimulation of the cardioaccelerator nerve at doses which did not alter the heart rate response to direct beta-adrenoceptor stimulation by isoproterenol (0.1 microgram/kg i.v.). The lowest doses of nifedipine (0.03 mg/kg) and verapamil (0.3 mg/kg) that produced decreases in mean arterial blood pressure were the same as or greater than those which selectivity reduced the tachycardiac effects of low frequency (1 Hz, 25-35 V, 5 ms), but not high frequency (10 Hz, 25-35 V, 5 ms) cardiac nerve stimulation. These data suggest that threshold vasodilator doses of some Ca2+ blockers may selectively reduce low level (or basal) sympathetic neurotransmission and this additional pharmacologic action may contribute to the antihypertensive mechanism. The failure to inhibit the high frequency nerve response may also help to explain the relatively low incidence of orthostatic hypotension associated with the clinical use of Ca2+ blockers as compared to other direct-acting vasodilators.
D000818:Animals; D001338:Autonomic Fibers, Postganglionic / Q000187:drug effects; D001340:Autonomic Nerve Block; D001794:Blood Pressure / Q000187:drug effects; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D002319:Cardiovascular System / Q000187:drug effects*; D004110:Diltiazem / Q000494:pharmacology; D004285:Dogs; D006329:Heart Conduction System / Q000187:drug effects; D006339:Heart Rate / Q000187:drug effects; D009543:Nifedipine / Q000494:pharmacology; D013564:Sympathetic Nervous System / Q000187:drug effects*; D014700:Verapamil / Q000494:pharmacology
D002121:Calcium Channel Blockers; D014700:Verapamil; D004110:Diltiazem; D009543:Nifedipine