This Article Full Text Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Katsuda, Y. Articles by Takeshita, A. Search for Related Content PubMed PubMed Citation Articles by Katsuda, Y. Articles by Takeshita, A.

(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

This article has been cited by other articles:

				H. M. O. Farouque, S. G. Worthley, and I. T. Meredith Effect of ATP-Sensitive Potassium Channel Inhibition on Coronary Metabolic Vasodilation in Humans Arterioscler. Thromb. Vasc. Biol., May 1, 2004; 24(5): 905 - 910. [Abstract] [Full Text]

				R. Nakamura, K. Egashira, K. Arimura, Y. Machida, T. Ide, H. Tsutsui, H. Shimokawa, and A. Takeshita Increased inactivation of nitric oxide is involved in impaired coronary flow reserve in heart failure Am J Physiol Heart Circ Physiol, December 1, 2001; 281(6): H2619 - H2625. [Abstract] [Full Text] [PDF]

				K. Arimura, K. Egashira, R. Nakamura, T. Ide, H. Tsutsui, H. Shimokawa, and A. Takeshita Increased inactivation of nitric oxide is involved in coronary endothelial dysfunction in heart failure Am J Physiol Heart Circ Physiol, January 1, 2001; 280(1): H68 - H75. [Abstract] [Full Text] [PDF]

				T. Tanikawa, H. Kanatsuka, R. Koshida, M. Tanaka, A. Sugimura, T. Kumagai, M. Miura, T. Komaru, and K. Shirato Role of pertussis toxin-sensitive G protein in metabolic vasodilation of coronary microcirculation Am J Physiol Heart Circ Physiol, October 1, 2000; 279(4): H1819 - H1829. [Abstract] [Full Text] [PDF]

				N. Matsuda, K. G. Morgan, and F. W. Sellke Effects of pinacidil on coronary Ca2+-myosin phosphorylation in cold potassium cardioplegia model Am J Physiol Heart Circ Physiol, September 1, 2000; 279(3): H882 - H888. [Abstract] [Full Text] [PDF]

				K. N. Richmond, J. D. Tune, M. W. Gorman, and E. O. Feigl Role of KATP+ channels and adenosine in the control of coronary blood flow during exercise J Appl Physiol, August 1, 2000; 89(2): 529 - 536. [Abstract] [Full Text] [PDF]

				K. N. Richmond, J. D. Tune, M. W. Gorman, and E. O. Feigl Role of K+ATP channels in local metabolic coronary vasodilation Am J Physiol Heart Circ Physiol, December 1, 1999; 277(6): H2115 - H2123. [Abstract] [Full Text] [PDF]

				C. E. Schotborgh and A. A.M. Wilde ATP-Sensitive Potassium Channel Openers and Blockers in the Cardiovascular System: Physiology, Pharmacology, and Clinical Effects Seminars in Cardiothoracic and Vascular Anesthesia, September 1, 1998; 2(3): 243 - 255. [Abstract] [PDF]

				K. Egashira, Y. Katsuda, M. Mohri, T. Kuga, T. Tagawa, T. Kubota, Y. Hirakawa, and A. Takeshita Role of Endothelium-Derived Nitric Oxide in Coronary Vasodilatation Induced by Pacing Tachycardia in Humans Circ. Res., August 1, 1996; 79(2): 331 - 335. [Abstract] [Full Text]