Comparative Actions of Dihydropyridine Slow Channel Calcium Blocking Agents in Conscious Dogs: Systemic and Coronary Hemodynamics with and Without Combined Beta Adrenergic Blockade

The cardiovascular effects of the dihydropyridine slow channel calcium blocking agents, nifedipine, nitrendipine, FR 34235, niludipine and nisoldipine were compared to the vasodilator, hydralazine, in conscious, instrumented dogs before and after propranolol (2 mg/kg i.v.). The calcium-blocking agents (1.0, 2.5, 5.0, 10.0 and 25.0 micrograms/kg/min i.v.) and hydralazine (0.01, 0.025, 0.05, 0.10 and 0.25 mg/kg/min i.v.) produced dose-related decreases in blood pressure and reflex increases in heart rate and heart rate-systolic pressure product, an index of myocardial oxygen consumption. Hydralazine also produced a reflex increase in myocardial contractility (+dP/dt); however, minimal changes in contractility were observed with the dihydropyridines. Nisoldipine, nitrendipine and FR 34235 were relatively more effective in reducing arterial pressure than niludipine, nifedipine and hydralazine. For any given reduction in pressure, hydralazine produced the greatest reflex tachycardia at low doses. Of the calcium channel blockers, nifedipine produced the greatest and niludipine the least reflex tachycardia. Propranolol attenuated the reflex increase in heart rate and rate-pressure product produced by all vasodilators studied. Only slight changes in global contractility were observed after combined use of the dihydropyridines and propranolol. Nisoldipine, FR 34235 and nifedipine produced the greatest coronary vasodilation whereas niludipine, nitrendipine and hydralazine were less effective. In addition, the dihydropyridines produced a greater increase in systolic than diastolic flow. The present results demonstrate that while all dihydropyridine calcium channel blocking agents exhibit many similarities, certain differences exist. Furthermore, the "reflex" tachycardia observed with these drugs was not solely related to the degree of reduction in arterial pressure.(ABSTRACT TRUNCATED AT 250 WORDS)