Effects of calcium-antagonistic coronary vasodilators on myocardial contractility and membrane potentials

Abstract

To clarify the relation between the negative inotropic effects of "calcium-antagonistic" vasodilators and their calcium-antagonistic effects, the effects of nifedipine, verapamil and diltiazem on isolated electrically-driven left atrial preparations of the guinea pig were studied. The ion-specificity of the antagonistic effects was also studied. In normal Tyrode's solution, all three vasodilators produced a shift to the right to the dose-response curve for calcium, the pA2 values being 5.90 for nifedipine, 4.88 for verapamil and 4.07 for diltiazem. The maximum rate of rise of action potentials recorded as a measure of the sodium permeability of the membrane was found to be reduced by verapamil and diltiazem, while this rate was unaffected by nifedipine. All three vasodilators suppressed the contractile activities induced in potassium-depolarized atria by isoproterenol and the dose-response curves for calcium were shifted to the right, the pA2 values being 8.24 for nifedipine, 6.67 for verapamil and 6.57 for diltiazem. In another set of experiments, calcium-dependent action potentials were evoked in the potassium-depolarized atria either by isoproterenol or aminophylline. These action potentials were suppressed by the above three vasodilators at dosage levels comparable to those producing suppression of the isoproterenol-induced contractile response of the depolarized atria.