title: Decreased expression of aortic KIR6.1 and SUR2B in hypertension does not correlate with changes in the functional role of K(ATP) channels.
abstract: ATP-dependent potassium (K(ATP)) channels are the target of multiple vasoactive factors and drugs. Changes in the functional role of ATP-dependent (K(ATP)) potassium channels in hypertension are controversial. The aim of the present study was to analyze the possible changes of ATP-sensitive potassium channels (K(ATP)) expression and function during hypertension. For this purpose, we used endothelium-denuded aorta segments from Wistar-Kyoto (WKY) and spontaneously hypertensive rats (SHR) to analyze the 1) expression of K(ATP) subunits Kir6.1, Kir6.2 and SUR2B by immunohistochemistry and Western blot, 2) the K(ATP) currents recorded in the whole cell configuration of the patch-clamp technique and 3) the vasodilator response to the K(ATP) channel openers, pinacidil and cromakalim. Kir6.1 and SUR2B were expressed in the medial layer of the aorta from WKY rats and SHR rats, while Kir6.2 was not detected in aorta from either strain. Kir6.1 and SUR2B expression were decreased in hypertension. However, the vasodilator responses of pinacidil and cromakalim were similar in WKY rats and SHR rats. Moreover, pinacidil induced increase in K+ currents was also similar in WKY rats and SHR rats and also similarly inhibited by glybenclamide. Our data demonstrate for the first time direct evidence of decreased aortic Kir6.1/SUR2B subunit expression in hypertension, but preserved functional responses to K(ATP) channel openers.
authors.affiliation: Department of Physiology, School of Medicine, Universidad Autonoma de Madrid, Spain.
authors.forename: Javier
authors.initials: J
authors.lastname: Blanco-Rivero
authors.forename: Carlos
authors.initials: C
authors.lastname: Gamallo
authors.forename: Rosa
authors.initials: R
authors.lastname: Aras-López
authors.forename: Laura
authors.initials: L
authors.lastname: Cobeño
authors.forename: Angel
authors.initials: A
authors.lastname: Cogolludo
authors.forename: Francisco
authors.initials: F
authors.lastname: Pérez-Vizcaino
authors.forename: Mercedes
authors.initials: M
authors.lastname: Ferrer
authors.forename: Gloria
authors.initials: G
authors.lastname: Balfagon
mesh_terms: D018528:ATP-Binding Cassette Transporters / Q000096:biosynthesis* / Q000235:genetics; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology; D001013:Aorta, Thoracic / Q000187:drug effects / Q000378:metabolism; D015153:Blotting, Western; D019806:Cromakalim / Q000494:pharmacology; D005905:Glyburide / Q000494:pharmacology; D006973:Hypertension / Q000378:metabolism*; D007004:Hypoglycemic Agents / Q000494:pharmacology; D007150:Immunohistochemistry; D054086:KATP Channels / Q000378:metabolism*; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000378:metabolism*; D018408:Patch-Clamp Techniques; D020110:Pinacidil / Q000494:pharmacology; D024661:Potassium Channels, Inwardly Rectifying / Q000096:biosynthesis* / Q000235:genetics; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D011955:Receptors, Drug / Q000096:biosynthesis* / Q000235:genetics; D064233:Sulfonylurea Receptors
chemical_list: D018528:ATP-Binding Cassette Transporters; D000959:Antihypertensive Agents; D007004:Hypoglycemic Agents; D054086:KATP Channels; D024661:Potassium Channels, Inwardly Rectifying; D011955:Receptors, Drug; D064233:Sulfonylurea Receptors; C092520:uK-ATP-1 potassium channel; D019806:Cromakalim; D020110:Pinacidil; D005905:Glyburide