Reflex chronotropic and inotropic effects of calcium channel-blocking agents in conscious dogs. Diltiazem, verapamil, and nifedipine compared.

In chronically instrumented, conscious dogs, rapid injection of equihypotensive doses of three calcium channel-blocking agents, verapamil (250 micrograms/kg), diltiazem (200 micrograms/kg) and nifedipine (50 micrograms/kg), produced disparate chronotropic and inotropic responses. Although they all decreased mean arterial pressure by about 10%, heart rate (93 +/- 4 beats/min) was markedly increased to 175 +/- 12 with nifedipine, to 163 +/- 15 with verapamil, and only slightly increased to 118 +/- 7 with diltiazem. Contractile responses measured before (left ventricular dP/dtmax, 2749 +/- 131 mm Hg/sec) and during left ventricular ejection (endocardial dimension dD/dtmax, 57 +/- 4 mm/sec) were increased by 24% and 14% with nifedipine, decreased by 26% and 22% with verapamil, and were unchanged with diltiazem. These chronotropic and inotropic responses to rapid intravenous administration of the three drugs were increased in a dose-dependent manner. Similar results also were observed after slow infusion of th...