COMPARATIVE ACTIONS OF DIHYDROPYRIDINE SLOW CHANNEL CALCIUM BLOCKING-AGENTS IN CONSCIOUS DOGS - ALTERATIONS IN BAROREFLEX SENSITIVITY

  • 1 January 1984
    • journal article
    • research article
    • Vol. 230  (2) , 376-382
Abstract
The effects of 5 dihydropyridine slow channel Ca blocking agents, nifedipine, nitrendipine, FR 34235 [2-cyano-1,4-dihydro-6-methyl-4-(3-nitrophenyl)-3,5-pyridinedicarboxylic acid 3-methyl 5-(1-methylethyl) ester], niludipine and nisoldipine, were compared to those of the peripheral vasodilator hydralaxzine on bradycardia and tachycardia after abrupt increases and decreases in arterial pressure in conscious dogs. On alternate days, the baroreflex was elicited during control conditions (drug vehicle) and/or after low (2.5 .mu.g/kg per min) or high (5.0 .mu.g/kg per min) equihypotensive doses of Ca antagonists or hydralazine (0.05 and 0.1 mg/kg per min). Baroreflexes were elicited by means of bolus injections of nitroprusside and phenylephrine. Certain of the dihydropyridine Ca channel blocking agents were found to interfere significantly with the reflex bradcardia after a rise in pressure, a phenomenon usually attributed to an increase in parasympathetic tone. Nisoldipine, niludipine and FR 34235 decreased baroreceptor sensitivity (defined as .DELTA. cardiac interval/.DELTA. systolic arterial pressure; ms/mm Hg in a dose-related manner. Nifedipine, nitrendipine and hydralazine had no significant effect. The dihydropyridines and hydralazine had little effect on baroreceptor-induced withdrawal of vagal tone or increases in sympathetic tone in response to sudden decreases in blood pressure. Ca antagonists with isopropyl substitution as part of the ester function of the dihydropyridine nucleus, nisoldipine, niludipine and FR 34235, interfered to a greater extent with the vagally mediated reduction in cardiac rate. Changes in baroreflex gain may provide a basis for differential actions of dihydropyridine Ca channel blockers on the magnitude of change in heart rate in response to an abrupt increase in arterial pressure.