EVIDENCE AGAINST K-ATP CHANNEL INVOLVEMENT IN ADENOSINE RECEPTOR-MEDIATED DILATION OF EPICARDIAL VESSELS

The purpose of this study was to determine whether ATP-glyburide-sensitive K+ (K-ATP-glyburide) channels are involved in the adenosine-induced vasorelaxation of porcine and canine epicardial vessels in vitro. Adenosine and its analogues, 2-chloroadenosine (CAD), 5'-N-ethylcarboxamidoadenosine (NECA), R-N-6-(2-phenylisopropyl)adenosine (R-PIA), N-6-cyclopentyladenosine (CPA), N-6-[2-(3,5-dimethoxyphenyl)-2-(2-methylphenyl)]adenosine (DPMA), 2-phenylaminoadenosine (CV-1808), 2-[m-(carboxyethyl)phenylamino]-5'-N-ethylcarboxamidoadenosine (CGS-22988), 2-[(2-cyclohexylethyl) amino]adenosine (CGS-22492), 2-[(p-amino)phenethylamino] adenosine (APE), and 2-(1-octynyl)adenosine (YT-146) (10 nM-100 mu M), produced concentration-dependent relaxations in endothelium-intact and -denuded arterial ring segments contracted with 30 mM KCl, 10 nM endothelin-1, or 10 mu M prostaglandin F-2 alpha. Sodium nitroprusside (SNP; 1 nM-10 mu M) and K-ATP-channel activator, pinacidil (10 nM-10 mu M), also produced similar vasodilatory responses. Glyburide, a K-ATP- channel blocker, caused a rightward shift of the concentration-response curve to pinacidil but did not alter the responses elicited by SNP or adenosine and its analogues. The data suggest that K-ATP-glyburide channels are not involved in the mechanism whereby adenosine and its analogues elicit their vasorelaxant response in isolated porcine or canine epicardial vessels.