Coronary reactive hyperemia and adenosine-induced vasodilation are mediated partially by a glyburide-sensitive mechanism.
The effect of glyburide on coronary reactive hyperemia and dilator responses to adenosine was evaluated in isolated perfused guinea pig hearts and anesthetized dogs. In isolated guinea pig hearts, changes in flow due to increasing concentrations of adenosine were measured, followed by 2 min of global ischemia to produce reactive hyperemia. This procedure was repeated after glyburide treatment. A similar study was performed in anesthetized open chest dogs. In isolated guinea pig hearts, 1 microM glyburide reduced reactive hyperemia with a peak flow reduction of 30.7% and debt repayment reduction of 78.0%, relative to vehicle-treated hearts. The adenosine dose-response curve in these hearts was shifted 20-fold to the right by 1 microM glyburide. Glyburide (3 mg/kg + 0.01 mg/kg/min) in dogs inhibited both the peak flow (from 154 +/- 26 to 105 +/- 22 ml/min) and the percentage of debt repayment (from 756 +/- 243 to 336 +/- 88%) of reactive hyperemia. Additionally, the canine intracoronary adenosine response curve was shifted rightward 100-fold by glyburide. Thus, there is a glyburide-sensitive component influencing the magnitude of both the adenosine and the reactive hyperemia response, suggesting that some of this response involves ATP-sensitive potassium channels.
Clayton
F C
FC
Department of Pharmacology, Bristol-Myers Squibb Pharmaceutical Research Institute, Princeton, N.J. 08543-4000.
Hess
T A
TA
Smith
M A
MA
Grover
G J
GJ
D000241:Adenosine / Q000494:pharmacology; D000818:Animals; D003326:Coronary Circulation / Q000187:drug effects; D004285:Dogs; D005260:Female; D005905:Glyburide / Q000494:pharmacology*; D006168:Guinea Pigs; D006940:Hyperemia / Q000188:drug therapy / Q000209:etiology* / Q000503:physiopathology; D066298:In Vitro Techniques; D008297:Male; D010477:Perfusion; D014664:Vasodilation / Q000187:drug effects*
D000241:Adenosine; D005905:Glyburide