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 (Glb), prevents metabolic coronary vasodilation associated with increased myocardial oxygen consumption (MVO2) 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 Glb. 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 x min-1) resulted in the sustained increase in CBF as well as in the myocardial inotropic and chronotropic state. Glb (10, 30, and 100 micrograms/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 Glb. 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 Glb. Intracoronary denopamine (0.1 microgram.kg-1 x min-1), a beta 1-selective agonist, increased CBF, which was almost completely abolished by Glb. The increases in MVO2 induced by Iso or denopamine were similar before and after Glb, indicating that attenuation of the Iso- or denopamine-induced increase in CBF by Glb did not result from the decrease in MVO2. These results indicate that Glb prevented the increase in CBF associated with increased MVO2 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.