Mechanisms underlying the cardiovascular action of a new dihydropyridine vasodilator YC-93

Abstract

1. The mechanisms underlying the cardiovascular action of YC-93, a new dihydropyridine vasodilator with cyclic AMP phosphodiesterase inhibitory activity, was investigated by comparing its effects with those of papaverine in various isolated, blood-perfused heart preparations of the dog. 2. In all preparations YC-93 injected into the nutrient arteries produced a dose-dependent increase in blood flow, and in this respect YC-93 was about twenty times more potent than papaverine on a weight basis. 3. In sinoatrial node preparations YC-93 injected into the sinus node artery decreased sinus rate in a dose-dependent manner, and in large doses produced atrial standstill. 4. In atrioventricular (a.v.) node preparations YC-93 injected into the a.v. node artery increased a.v. conduction time in a dose-dependent manner, and in large doses produced a second or third degree block of a.v. conduction. However YC-93 injected into the anterior septal artery scarcely affected a.v. conduction. 5. In spontaneously contracting papillary muscle preparations YC-93 injected into the anterior septal artery failed to affect ventricular automaticity in doses which markedly decreased developed tension of papillary muscles. 6. In papillary muscle preparations driven at a fixed rate YC-93 injected into the anterior septal artery produced a dose-dependent decrease in developed tension of papillary muscles. 7. Unlike YC-93, papaverine decreased a.v. conduction time in a.v. node preparations and increased developed tension of papillary muscle preparations. 8. The cardiac effects of YC-93 elucidated in the present experiments are characteristic of calcium-antagonistic vasodilators. The action of YC-93 as an inhibitor of cyclic AMP phosphodiesterase does not appear to play a role in its cardiac action.