Comparative actions of dihydropyridine slow channel calcium blocking agents in conscious dogs: alterations in...

The effects of five dihydropyridine slow channel calcium blocking agents, nifedipine, nitrendipine, FR 34235, niludipine and nisoldipine were compared to those of the peripheral vasodilator hydralazine on the reflex 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 micrograms/kg/min) or high (5.0 micrograms/kg/min) equihypotensive doses of calcium antagonists or hydralazine (0.05 and 0.1 mg/kg/min). Baroreflexes were elicited by means of bolus injection of nitroprusside and phenylephrine. Certain of the dihydropyridine calcium channel blocking agents were found to interfere significantly with the reflex bradycardia 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; milliseconds per millimeter of mercury) in a dose-related manner. On the other hand, 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. Calcium antagonists with isopropyl substitution as part of the ester function on 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 calcium channel blockers on the magnitude of change in heart rate in response to an abrupt increase in arterial pressure.