Glibenclamide, a Selective Inhibitor of ATP-Sensitive K + Channels, Attenuates Metabolic Coronary Vasodilatation Induced by Pacing Tachycardia in Dogs

Abstract

Background We previously reported that glibenclamide (a selective inhibitor of ATP-sensitive K + channels [K + ATP channels]) inhibited metabolic coronary vasodilatation induced by β 1 -adrenoceptor stimulation. However, the role of K + ATP channels in metabolic coronary vasodilatation induced by tachycardia is still unknown. This study aimed to determine whether glibenclamide attenuates metabolic coronary vasodilatation induced by pacing-induced tachycardia. Methods and Results In anesthetized dogs, increasing heart rate from 103±1 to 160 beats per minute with atrial pacing increased coronary blood flow without altering arterial pressure and left ventricular pressure. Intracoronary infusion of glibenclamide at 1.5 and 5.0 μg · kg −1 · min −1 did not alter basal coronary blood flow but significantly attenuated ( P <.01) the tachycardia-induced coronary vasodilatation without altering the tachycardia-induced increase in myocardial oxygen consumption (MV̇ o 2 ). In conscious dogs, intracoronary glibenclamide at 5.0 μg · kg −1 · min −1 attenuated ( P <.05) coronary vasodilatation induced by ventricular pacing from 85±6 to 150 beats per minute. Glibenclamide markedly attenuated coronary vasodilatation evoked with the K + ATP channel opener pinacidil. Conclusions These data indicate that blockade of coronary vascular K + ATP channels with glibenclamide inhibited metabolic coronary vasodilatation induced by pacing tachycardia in dogs, suggesting that K + ATP channels are involved in the mechanism mediating metabolic coronary vasodilatation associated with pacing tachycardia.