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(Circulation. 1995;92:511-517.)
© 1995 American Heart Association, Inc.

Articles

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

Yousuke Katsuda, MD; Kensuke Egashira, MD; Hideki Ueno, MD; Yutaka Akatsuka, MD; Takahiro Narishige, MD; Yukinori Arai, PhD; Tsuneo Takayanagi, BS; Hiroaki Shimokawa, MD; Akira Takeshita, MD

From the Research Institute of Angiocardiology and Cardiovascular Clinic, Kyushu University School of Medicine, Fukuoka, Japan.

Correspondence to Kensuke Egashira, MD, PhD, The Research Institute of Angiocardiology and Cardiovascular Clinic, Kyushu University School of Medicine, 3-1-1 Maidashi, Higashi-ku, Fukuoka, 812, Japan.

Background We previously reported that glibenclamide (a selective inhibitor of ATP-sensitive K⁺ channels [K⁺_ATP channels]) inhibited metabolic coronary vasodilatation induced by ß₁-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 (MO₂). 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.

Key Words: adenosine • potassium • circulation • glibenclamide • vasodilation

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