2-Deoxyglucose-induced vasodilation and hyperpolarization in rat coronary artery are reversed by glibenclamide.
The mechanisms responsible for coronary vasodilation during ischemia or hypoxia are poorly understood. It has recently been suggested that alterations in intracellular ATP may play a role in this response. We examined whether dilation of isolated coronary arteries in response to metabolic blockade by 2-deoxyglucose, which competitively inhibits glycolysis and glycogenolysis, was sensitive to glibenclamide, an inhibitor of ATP-sensitive potassium channels. Pressurized rat coronary arteries with myogenic tone dilated in response to 2-deoxyglucose by an endothelium-independent mechanism. The dilation was accompanied by a substantial hyperpolarization. Addition of glibenclamide partially reversed this vasodilation and abolished the hyperpolarization. We propose that ATP-sensitive potassium channels play a significant role in the dilator response to 2-deoxyglucose. This may have implications both for ischemia-induced coronary vasodilation and for the use of oral hypoglycemic agents in general.
Conway
M A
MA
Department of Pharmacology, University of Vermont, Colchester 05446.
Nelson
M T
MT
Brayden
J E
JE
D000818:Animals; D001578:Benzopyrans / Q000494:pharmacology; D003331:Coronary Vessels / Q000187:drug effects* / Q000502:physiology; D019806:Cromakalim; D003847:Deoxyglucose / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004594:Electrophysiology; D005260:Female; D005905:Glyburide / Q000494:pharmacology*; D008297:Male; D026902:Potassium Channel Blockers; D011758:Pyrroles / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D014664:Vasodilation
D001578:Benzopyrans; D026902:Potassium Channel Blockers; D011758:Pyrroles; D019806:Cromakalim; D003847:Deoxyglucose; D005905:Glyburide