Glibenclamide, a selective inhibitor of ATP-sensitive K+ channels, attenuates metabolic coronary vasodilatation induced by pacing tachycardia in dogs

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

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    29 Citations (Scopus)

    Abstract

    Background: We previously reported that glibenclamide (a selective inhibitor of ATP-sensitive K+ channels [K+(ATP) channels) inhibited metabolic coronary vasodilatation induced by β1-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 (MV̇O2). 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.

    Original languageEnglish
    Pages (from-to)511-517
    Number of pages7
    JournalCirculation
    Volume92
    Issue number3
    DOIs
    Publication statusPublished - Aug 1 1995

    All Science Journal Classification (ASJC) codes

    • Cardiology and Cardiovascular Medicine
    • Physiology (medical)

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