ATP-sensitive potassium channels in the basilar artery during chronic hypertension.
We examined the hypothesis that dilatation of the basilar artery in response to activation of ATP-sensitive potassium channels is impaired in stroke-prone spontaneously hypertensive rats (SHRSP). Changes in basilar artery diameter in response to aprikalim, a direct activator of ATP-sensitive potassium channels, were measured in anesthetized SHRSP and normotensive Wistar-Kyoto (WKY) rats through a cranial window. Topical application of aprikalim increased basilar artery diameter in WKY rats. Glibenclamide, a selective inhibitor of ATP-sensitive potassium channels, abolished aprikalim-induced vasodilatation. Thus, ATP-sensitive potassium channels are functional in the basilar artery of WKY rats in vivo. Aprikalim (10(-6) mol/L) dilated the basilar artery by 31 +/- 5% (mean +/- SEM) in WKY rats but only 5 +/- 1% in SHRSP. The concentration-response curve to aprikalim in SHRSP was significantly shifted to the right, but the response to the highest concentration of aprikalim (10(-5.5) mol/L) was similar in SHRSP and WKY rats. Vasodilatation in response to norepinephrine was also impaired in SHRSP. Dilator responses of the basilar artery to forskolin, a direct activator of adenylate cyclase, and nitroprusside, a direct activator of guanylate cyclase, were normal in SHRSP. The findings suggest that dilatation of the basilar artery in response to direct activation of ATP-sensitive potassium channels is impaired in SHRSP compared with WKY rats in vivo.
Kitazono
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Department of Internal Medicine, University of Iowa College of Medicine, Iowa City 52242.
Heistad
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Faraci
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D000255:Adenosine Triphosphate / Q000494:pharmacology*; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology; D001488:Basilar Artery / Q000187:drug effects / Q000502:physiology / Q000503:physiopathology*; D002561:Cerebrovascular Disorders / Q000235:genetics; D005576:Colforsin / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D006973:Hypertension / Q000235:genetics / Q000503:physiopathology*; D066298:In Vitro Techniques; D008297:Male; D008955:Models, Cardiovascular; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000502:physiology / Q000503:physiopathology; D009599:Nitroprusside / Q000494:pharmacology; D009638:Norepinephrine / Q000494:pharmacology; D010847:Picolines / Q000494:pharmacology*; D015221:Potassium Channels / Q000187:drug effects / Q000378:metabolism*; D011714:Pyrans / Q000494:pharmacology*; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D014664:Vasodilation / Q000187:drug effects*
D000959:Antihypertensive Agents; D010847:Picolines; D015221:Potassium Channels; D011714:Pyrans; D009599:Nitroprusside; D005576:Colforsin; C061043:aprikalim; D000255:Adenosine Triphosphate; D009638:Norepinephrine