title: 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 beta 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.
  
  
  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 micrograms.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 (MVO2). In conscious dogs, intracoronary glibenclamide at 5.0 micrograms.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 vasodilation 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.
authors.affiliation: Research Institute of Angiocardiology, Kyushu University School of Medicine, Fukuoka, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Katsuda
authors.forename: K
authors.initials: K
authors.lastname: Egashira
authors.forename: H
authors.initials: H
authors.lastname: Ueno
authors.forename: Y
authors.initials: Y
authors.lastname: Akatsuka
authors.forename: T
authors.initials: T
authors.lastname: Narishige
authors.forename: Y
authors.initials: Y
authors.lastname: Arai
authors.forename: T
authors.initials: T
authors.lastname: Takayanagi
authors.forename: H
authors.initials: H
authors.lastname: Shimokawa
authors.forename: A
authors.initials: A
authors.lastname: Takeshita
mesh_terms: D000255:Adenosine Triphosphate / Q000502:physiology; D000818:Animals; D002304:Cardiac Pacing, Artificial; D003331:Coronary Vessels / Q000503:physiopathology*; D004285:Dogs; D005905:Glyburide / Q000627:therapeutic use*; D026902:Potassium Channel Blockers; D013610:Tachycardia / Q000188:drug therapy* / Q000503:physiopathology; D014664:Vasodilation / Q000187:drug effects*
chemical_list: D026902:Potassium Channel Blockers; D000255:Adenosine Triphosphate; D005905:Glyburide