THE ROLE OF ATP-SENSITIVE POTASSIUM CHANNELS IN THE MECHANISMS OF METABOLIC CORONARY VASODILATION

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1) Effects of glibenclamide (an inhibitor of ATP-sensitive potassium channels) on metabolic coronary vasodilationExperiments were performed in anesthetized and conscious dogs. Increasing heart rate from 100 to 160 bpm increased coronary blood flow without altering other hemodynamic parameters. Glibenclamide (1.5 and 5.0 mug/kg・min) significantly inhibited coronary vasodilation induced by pacing tachycardia, while it did not affect coronary vasodilation induced by acetylcholine and nitroglycerin. Glibenclamide completely abolished coronary vasodilation induced by pinacidil. These results suggest that metabolic coronary vasodilation is mediated at least in part by ATP-sensitive potassium channels.2) Effects of Pinacidil (ATP-sensitive potassium channel opener) on metabolic coronary vasodilationExperiments were performed in anesthetized dogs. Intracoronary infusion of denopamine (a selective beta1-adrenoceptor agonist) increased coronary blood flow associated with an increase in myocardial inotropic state. Pinacidil 1 mug/min, that had no effects on basal hemodynamic parameters but modestly increased coronary blood flow by 10% or less, augmented coronary vasodilation induced by denopamine, while denopamine-induced changes in myocardial inotropic state and myocardial oxygen consumption were comparable before and after pinacidil.Pinacidil did not affect coronary vasodilation induced by acetylcholine, nitroglycerin, and beta2-adrenoceptor stimulation. Denopamine-induced coronary vasodilation was completely inhibited by a selective beta1 adrenoceptor antagonist bisoprolol. These results suggest that ATP-sensitive potassium channel opener pinacidil augments metabolic coronary vasodilation induced by beta1-adrenoceptor stimulation.