ATP-sensitive K+ channel opener pinacidil augments beta(1)-adrenoceptor-induced coronary vasodilation in dogs

The opening of ATP-sensitive K+ (K-ATP(+)) channels contributes to the mechanism of metabolic coronary vasodilation. The aim of the present study was to determine whether K-ATP(+) channel opener pinacidil augments coronary vasodilation induced by beta-adrenoceptor stimulation. In anesthetized dogs, coronary vasodilation in response to intracoronary infusion of a beta(1)-adrenoceptor agonist denopamine, selective beta(2)-adrenoceptor stimulation with isoproterenol after bisoprolol or nitroglycerin was studied before and during simultaneous intracoronary infusion of pinacidil at a dose of 1 mu g/min, which had no effect on basal hemodynamics. Pinacidil augmented the denopamine-induced increase in coronary blood flow (CBF) from 38 +/- 9 to 66 +/- 16% (P < 0.05) but did not affect the denopamine-induced increase in myocardial oxygen consumption (MV(O)2). Pinacidil had no effect on the increases in CBF or MV(O)2 induced by isoproterenol or nitroglycerin. Thus pinacidil selectively augmented beta(1)-adrenoceptor-mediated coronary vasodilation. These observations suggest that the K-ATP(+) channel opener pinacidil may increase myocardial perfusion during metabolic stress associated with beta(1)-adrenoceptor stimulation.