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 adenosine analogues on porcine coronary artery in vitro. In both endothelium- intact and -denuded rings, 5'-(N-ethylcarboxamido)adenosine (NECA), 2-[p-(2- carboxyethyl)]phenylethylamino-5'-N-ethylcarboxamidoadenosine (CGS-21680), 2- chloroadenosine (CAD), N⁶-R-phenylisopropyladenosine (R-PIA), 2- phenylaminoadenosine (PAA), N⁶-cyclohexyladenosine (CHA), N⁶- cyclopentyladenosine (CPA), and N⁶-S-phenylisopropyladenosine (S-PIA) produced concentration-dependent relaxations. The rank order of potency was consistent with A₂-adenosine receptor identification. The xanthine adenosine antagonist, 8-(sulfophenyl)theophylline (8-SPT), attenuated the relaxant 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 preparations. 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 the responses to NECA and CGS-21680. The adenosine receptor agonist, CGS-22988, also relaxed the denuded rings in a manner insensitive to blockade by 8-SPT. The data suggest that multiple A₂-adenosine receptors exist on the smooth muscle and endothelium of porcine coronary artery, mediating relaxation. Whereas the smooth muscle contains both xanthine-sensitive and -insensitive A₂-receptors, which can be activated by a wide range of adenosine agonists, the endothelium possesses xanthine-sensitive receptors that can be stimulated selectively by certain adenosine agonists, including 5'-uronamide derivatives, such as NECA and CGS- 21680. The smooth muscle also appears to contain xanthine-insensitive A₄- receptors activated by CGS-22988.