COMPARATIVE ACTIONS OF DIHYDROPYRIDINE SLOW CHANNEL CALCIUM BLOCKING-AGENTS IN CONSCIOUS DOGS - SYSTEMIC AND CORONARY HEMODYNAMICS WITH AND WITHOUT COMBINED BETA-ADRENERGIC-BLOCKADE

  • 1 January 1984
    • journal article
    • research article
    • Vol. 230  (2) , 367-375
Abstract
The cardiovascular effects of the dihydropyridine slow channel Ca2 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 Ca2-blocking agents (1.0, 2.5, 5.0, 10.0 and 25.0 .mu.g/kg per min i.v.) and hydralazine (0.01, 0.025, 0.05, 1.10 and 0.25 mg/kg per 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 O2 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 Ca2 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; niludipine, nitrendipine and hydralazine were less effective. In addition, the dihydropyridines produced a greater increase in systolic than diastolic flow. While all dihydropyridine Ca2 channel blocking agents exhibit many similarities, certain differences exist. Furthermore, the "reflex" tachycardia observed was not solely related to the degree of reduction in arterial pressure. Negative inotropic properties of the dihydropyridines were minimal in combination with propranolol. Greater decreases in systolic pressure were observed with a combination of propranolol plus the dihydropyridines than with the slow channel Ca2 blockers alone.

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