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-sensi tive K+ (K-ATP-glyburide) channels are involved in the adenosine-induc ed vasorelaxation of porcine and canine epicardial vessels in vitro. A denosine and its analogues, 2-chloroadenosine (CAD), 5'-N-ethylcarboxa midoadenosine (NECA), R-N-6-(2-phenylisopropyl)adenosine (R-PIA), N-6- cyclopentyladenosine (CPA), (3,5-dimethoxyphenyl)-2-(2-methylphenyl)]a denosine (DPMA), 2-phenylaminoadenosine (CV-1808), yethyl)phenylamino] -5'-N-ethylcarboxamidoadenosine (CGS-22988), 2-[(2-cyclohexylethyl) am ino]adenosine (CGS-22492), 2-[(p-amino)phenethylamino] adenosine (APE) , and 2-(1-octynyl)adenosine (YT-146) (10 nM-100 mu M), produced conce ntration-dependent relaxations in endothelium-intact and -denuded arte rial ring segments contracted with 30 mM KCl, 10 nM endothelin-1, or 1 0 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 produc ed similar vasodilatory responses. Glyburide, a K-ATP- channel blocker , caused a rightward shift of the concentration-response curve to pina cidil 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 v essels.