Effects of Bay k 8644 on the Coronary Vascular Selectivity of the Dihydropyridine Ca Antagonists in the Canine Isolated, Blood-Perfused Papillary Muscle Preparation

Antagonism by Bay k 8644 of the coronary vasodilator and negative inotropic effects of Ca antagonists was simultaneously investigated in the canine isolated, blood-perfused papillary muscle electrically driven at 2 Hz. Drugs were given intraarterially. Continuously infused intraarterially, Bay k 8644 inhibited more predominantly the coronary vasodilator effects of the dihydropyridine Ca antagonists (nifedipine, nitrendipine, and nicardipine) than those of diltiazem and verapamil, or the negative inotropic effects of nifedipine and nitrendipine. The negative inotropic effects of nicardipine, diltiazem, and verapamil were not significantly affected by Bay k 8644. The dose ratio for producing a 50% decrease in developed tension of the papillary muscle over the dose for producing a 50% increase in coronary blood flow (which reflects vascular selectivity) were 41 for nitrendipine, 25 for nifedipine, 21 for nicardipine, 9 for diltiazem, and 7 for verapamil. During infusion by Bay k 8644, the ratio was small (2 to 6) and almost similar among all five Ca antagonists. These results indicate that Bay k 8644 antagonizes more effectively the coronary vasodilating effects of the dihydropyridine Ca antagonists, suggesting that there is a specific type of Ca channel on coronary vascular smooth muscles, through which the dihydropyridine Ca antagonists act.