Adenosine receptor-mediated relaxation of porcine coronary artery in presence and absence of endothelium

Abstract

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-ethylcarboxamidoadenos ine (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 (Kb) 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.(ABSTRACT TRUNCATED AT 250 WORDS)

Cardiac purinergic signalling in health and disease

“…It was proposed that there was another P1R subtype, in addition to A2R, located on smooth muscle [431] since N 6 -cyclopentyladenosine, an A1R-selective agonist, had vasorelaxant activity in porcine and canine coronary arteries [432,433] and A1R are expressed by smooth muscle cells isolated from the porcine coronary artery [434], which also express A2R [435]. Adenosine-mediated relaxation in human small coronary arteries via A2BR, which was independent of the endothelium and NO [436].…”

Adenosine A2A receptor modulates vascular response in soluble epoxide hydrolase-null mice through CYP-epoxygenases and PPARγ

“…THE PHYSIOLOGICAL EFFECTS of adenosine have been observed in nearly every tissue and organ (1,19,(32)(33)(34)(35)53). Adenosine plays an important role in cardiac protection (15)(16)(17), as well as the maintenance of vascular tone via activation of four receptor subtypes (A 1 , A 2A , A 2B , and A 3 ).…”

Adenosine A2A receptor modulation of juvenile female rat skeletal muscle microvessel permeability

“…ADO-induced changes in vascular tone (magnitude, duration, and direction) differ with respect to the species, tissue, and receptor subtypes. In pig heart, ADO causes vasodilation primarily via activation of A 2A receptors (2,4,20), although A 1 , A 2A , and A 2B receptors are expressed in coronary vasculature (21,41). In mice, ADO-induced coronary vasodilatation is mediated by a combination of A 1 and/or A 3 receptors (53,54).…”