ADENOSINE RECEPTOR-MEDIATED RELAXATION OF PORCINE CORONARY-ARTERY IN PRESENCE AND ABSENCE OF ENDOTHELIUM

This study was designed to investigate the effects of a series of aden osine analogues on porcine coronary artery in vitro. In both endotheli um-intact and -denuded rings, 5'-(N-ethylcarboxamido)adenosine (NECA), l)]phenylethylamino-5'-N-ethylcarboxamidoadenosine (CGS-21680), 2-chl oroadenosine (CAD), N-6-R-phenylisopropyladenosine (R-PIA), 2-phenylam inoadenosine (PAA), N-6-cyclohexyladenosine (CHA), N-6-cyclopentyladen osine (CPA), and N-6-S-phenylisopropyladenosine (S-PIA) produced conce ntration-dependent relaxations. The rank order of potency was consiste nt with A(2)-adenosine receptor identification. The xanthine adenosine antagonist, 8-(sulfophenyl)theophylline (8-SPT), attenuated the relax ant responses to all the agonists in the endothelium-intact rings and to only CAD, R-PIA, PAA, CHA, CPA, and S-PIA in the denuded preparatio ns. Except for NECA and CGS-21680, the slopes of the relaxation curves and the dissociation constant (K-b) values for 8-SPT were similar for all agonists. In addition, endothelium removal selectively reduced th e responses to NECA and CGS-21680. The adenosine receptor agonist, CGS -22988, also relaxed the denuded rings in a manner insensitive to bloc kade by 8-SPT. The data suggest that multiple A(2)-adenosine receptors exist on the smooth muscle and endothelium of porcine coronary artery , mediating relaxation. Whereas the smooth muscle contains both xanthi ne-sensitive and -insensitive A(2)-receptors, which can be activated b y a wide range of adenosine agonists, the endothelium possesses xanthi ne-sensitive receptors that can be stimulated selectively by certain a denosine agonists, including 5'-uronamide derivatives, such as NECA an d CGS-21680. The smooth muscle also appears to contain xanthine-insens itive A(4)-receptors activated by CGS-22988.