Decreased expression of aortic KIR6.1 and SUR2B in hypertension does not correlate with changes in the functional role of KATP channels

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. (C) 2008 Elsevier B.V. All rights reserved.