ATP-sensitive potassium channels in isolated rat aorta during physiologic, hypoxic, and low-glucose conditions.
In arterial smooth muscle, adenosine triphosphate (ATP)-sensitive potassium channels are the targets of a variety of synthetic and endogenous vasodilators. In this study, we evaluated the influence of glibenclamide, an ATP-sensitive K(+)-channel blocker, on various vasodilator responses, including those by levcromakalim under hypoxic and low-glucose conditions in isolated rat aortic rings. The concentration-response curves induced by methacholine and sodium nitroprusside (after precontraction with 1 microM phenylephrine) were not affected by glibenclamide. Glibenclamide influenced neither the adenosine- nor the iloprost- (a stable prostacyclin) induced vasodilator effects. Glibenclamide caused a concentration-dependent rightward shift of the concentration-response curves of levcromakalim. The vascular tone induced by phenylephrine was not affected under low-glucose conditions, whereas hypoxia caused a decrease in the phenylephrine-induced contraction when compared with that under normal circumstances. Under all conditions, glibenclamide did not influence the phenylephrine-induced increase in vascular tone. Under low-glucose and hypoxic conditions, the concentration-response curves for levcromakalim showed a significantly less steep slope than under normal conditions, and higher concentrations of glibenclamide were necessary to inhibit the vasodilator response induced by levcromakalim under these experimental conditions adopted to mimic pathologic conditions. In conclusion, methacholine, sodium nitroprusside, adenosine, and iloprost appear not to induce vasodilation in the rat aorta by glibenclamide-sensitive K+ channels, whereas hypoxia and low-glucose levels cause an impaired function of the glibenclamide-sensitive K+ channels.
Hüsken
B C
BC
Department of Pharmacotherapy, University of Amsterdam, The Netherlands.
Pfaffendorf
M
M
van Zwieten
P A
PA
D000255:Adenosine Triphosphate / Q000502:physiology; D000818:Animals; D001013:Aorta, Thoracic / Q000378:metabolism*; D001578:Benzopyrans / Q000494:pharmacology; D019806:Cromakalim; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000502:physiology; D005905:Glyburide / Q000494:pharmacology*; D007003:Hypoglycemia / Q000378:metabolism*; D000860:Hypoxia / Q000378:metabolism*; D066298:In Vitro Techniques; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000378:metabolism*; D015221:Potassium Channels / Q000187:drug effects / Q000378:metabolism*; D011758:Pyrroles / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D014664:Vasodilation / Q000187:drug effects; D014665:Vasodilator Agents / Q000494:pharmacology
D001578:Benzopyrans; D015221:Potassium Channels; D011758:Pyrroles; D014665:Vasodilator Agents; D019806:Cromakalim; D000255:Adenosine Triphosphate; D005905:Glyburide