GLIBENCLAMIDE, A SELECTIVE INHIBITOR OF ATP-SENSITIVE K+ CHANNELS, ATTENUATES METABOLIC CORONARY VASODILATATION INDUCED BY PACING TACHYCARDIA IN DOGS

Background We previously reported that glibenclamide (a selective inhi bitor of ATP-sensitive K+ channels [K-ATP(+) channels]) inhibited meta bolic coronary vasodilatation induced by beta(1)-adrenoceptor stimulat ion. However, the role of K-ATP(+) channels in metabolic coronary vaso dilatation induced by tachycardia is still unknown. This study aimed t o determine whether glibenclamide attenuates metabolic coronary vasodi latation induced by pacing-induced tachycardia. Methods and Results In anesthetized dogs, increasing heart rate from 103+/-1 to 160 beats pe r minute with atrial pacing increased coronary blood flow without alte ring arterial pressure and left ventricular pressure. Intracoronary in fusion of glibenclamide at 1.5 and 5.0 mu g . kg(-1). min(-1) did not alter basal coronary blood flow but significantly attenuated (P<.01) t he tachycardia-induced coronary vasodilatation without altering the ta chycardia-induced increase in myocardial oxygen consumption (MVO(2)). In conscious dogs, intracoronary glibenclamide at 5.0 mu g . kg(-1). m in(-1) attenuated (P<.05) coronary vasodilatation induced by ventricul ar pacing from 85+/-6 to 150 beats per minute. Glibenclamide markedly attenuated coronary vasodilatation evoked with the K-ATP(+) channel op ener pinacidil. Conclusions These data indicate that blockade of coron ary vascular K-ATP(+) channels with glibenclamide inhibited metabolic coronary vasodilatation induced by pacing tachycardia in dogs, suggest ing that K-ATP(+) channels are involved in the mechanism mediating met abolic coronary vasodilatation associated with pacing tachycardia.