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 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.
Katsuda
Y
Y
Research Institute of Angiocardiology, Kyushu University School of Medicine, Fukuoka, Japan.
Egashira
K
K
Ueno
H
H
Akatsuka
Y
Y
Narishige
T
T
Arai
Y
Y
Takayanagi
T
T
Shimokawa
H
H
Takeshita
A
A
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*
D026902:Potassium Channel Blockers; D000255:Adenosine Triphosphate; D005905:Glyburide