Cardiovascular effects of the nifedipine analog, CGP 28 392, in the conscious dog.

The cardiovascular profile of the nifedipine analog, CGP 28 392, was studied in instrumented conscious dogs. CGP 28 392 (25, 50, 100, and 150 micrograms/kg) was administered intravenously, and systemic and coronary hemodynamics monitored with and without prior treatment with nifedipine, phentolamine, propranolol, or atropine. CGP 28 392 increased arterial blood pressure and coronary vascular resistance in a dose-related manner and reduced heart rate. No positive inotropic actions were observed. All hemodynamic effects of CGP 28 392 were blocked by nifedipine but were unaltered by phentolamine. The decrease in heart rate was attenuated by atropine and propranolol. These data demonstrate that the actions of CGP 28 392 are diametrically opposed to those of the dihydropyridine slow channel calcium entry blockers and are specifically blocked by nifedipine. The cardiovascular actions of this compound (with the exception of bradycardia) are not mediated through the autonomic nervous system, and interactions with other pharmacological agents suggest that CGP 28 392 has calcium channel activating properties.