Hyperpolarization and relaxation of resistance arteries in response to adenosine diphosphate. Distribution and mechanism of action.
Membrane hyperpolarization appears to be an important mechanism of vasodilation induced by many pharmacological and endogenous vasodilators. The objective of the present study was to determine the mechanisms of vasodilation induced by ADP, and endogenous vasodilator, in various resistance arteries isolated from the rabbit. ADP hyperpolarized (12-15 mV) and relaxed mesenteric and skeletal muscle resistance arteries. The hyperpolarization was abolished by glibenclamide, an inhibitor of ATP-sensitive potassium channels. Glibenclamide inhibited part of the ADP-induced relaxations of these arteries; thus, a portion of the relaxation appears to result directly from the change in membrane potential. Hyperpolarizations and relaxations to low concentrations of ADP (less than 0.3 microM) were abolished by removal of the endothelium, but responses to higher concentrations of ADP were partially independent of the endothelium. ADP did not hyperpolarize but did relax small-diameter middle cerebral arteries, and glibenclamide had no effect on these ADP-induced relaxations. Relaxations of small cerebral arteries to all concentrations of ADP were endothelium dependent. These studies support the hypothesis that activation of ATP-sensitive potassium channels is an important general mechanism of vasodilation, including responses of resistance arteries. However, this generalization may not apply to small pial arteries of the rabbit.
Department of Pharmacology, University of Vermont, Burlington 05405.
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Brayden
D000109:Acetylcholine / Q000494:pharmacology; D000244:Adenosine Diphosphate / Q000494:pharmacology*; D000818:Animals; D001158:Arteries / Q000187:drug effects* / Q000502:physiology; D002536:Cerebral Arteries / Q000187:drug effects / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D004594:Electrophysiology; D004730:Endothelium, Vascular / Q000166:cytology / Q000502:physiology; D005905:Glyburide / Q000494:pharmacology; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects*; D009132:Muscles / Q000098:blood supply; D011817:Rabbits; D013152:Splanchnic Circulation / Q000187:drug effects; D014664:Vasodilation / Q000187:drug effects
D000244:Adenosine Diphosphate; D000109:Acetylcholine; D005905:Glyburide