GLIBENCLAMIDE PREVENTS CORONARY VASODILATION INDUCED BY BETA(1)-ADRENOCEPTOR STIMULATION IN DOGS

This study aimed to determine whether a putative ATP-sensitive K+-channel blocker, glibenclamide (Gib), prevents metabolic coronary vasodilation associated with increased myocardial oxygen consumption (MVo(2)) caused by beta(1)-adrenoceptor stimulation in anesthetized open-chest dogs. Isoproterenol (Iso) was infused selectively into the left circumflex coronary artery before and after Gib. Coronary blood flow (CBF) by an electromagnetic flowmeter, regional myocardial function by sonomicrometers, and left ventricular and arterial pressures were continuously measured. An intracoronary infusion of Iso (10 ng.kg(-)1.min(-1)) resulted in the sustained increase in CBF as well as in the myocardial inotropic and chronotropic state. Gib (10, 30, and 100 mu g/min ic) attenuated the Iso-induced increase in CBF in a dose-dependent manner, whereas inotropic and chronotropic responses to Iso were not affected by Gib. After beta(1)-blockade with bisoprolol (0.3 mg/kg), which completely inhibited inotropic and chronotropic responses to Iso, the Iso-induced increase in CBF, presumably mediated by vascular beta 2-receptor stimulation, was not affected by Gib. Intracoronary denopamine (0.1 mu g.kg(-1). min-l), a beta(1)-selective agonist, increased CBF, which was almost completely abolished by Gib. The increases in MVo(2) induced by Iso or denopamine were similar before and after Gib, indicating that attenuation of the Iso- or denopamine-induced increase in CBF by Gib did not result from the decrease in MVo(2). These results indicate that Gib prevented the increase in CBF associated with increased MVo(2) caused by beta(1)-adrenoceptor stimulation. It is suggested that ATP-sensitive K+ channels may play an important role in metabolic coronary vasodilation in dogs.