Anales RANF

P.89 THE ACTIVATION OF ADENOSINE A2A BUT NOT A2B RECEPTORS IS INVOLVED IN URIDINE ADENOSINE TETRAPHOSPHATE-MEDIATED CORONARY SMOOTH MUSCLE RELAXATION C. Sun 1 , T. Jiao 2 , D. Merkus 3 , D.J. Duncker 3 , S.J. Mustafa 1 , Z. Zhou 1,2 1 . West Virginia University, Morgantown, WV, USA; 2 . Karolinska Institutet, Stockholm, Sweden; 3 . Erasmus University Medical Center, Rotterdam, The Netherlands. Activation of both adenosine A 2A and A 2B receptors contributes to coronary vasodilation. We previously demonstrated that uridine adenosine tetraphosphate (Up 4 A) is a novel vasodilator in the porcine coronary microcirculation, acting mainly on A 2A receptors and partially on P2 receptors. A major part of vasodilation produced by Up 4 A is mediated by smooth muscle cell (SMC) relaxation and activation of SMC A 2A receptors. Here, we further investigated whether activation of SMC A 2B or P2 receptors is involved in Up 4 A-mediated coronary relaxation. Both A 2A R and A 2B R may stimulate H 2 O 2 production leading to activation of K ATP channels in SMCs, we also studied the involvement of H 2 O 2 and K ATP channels in Up 4 A-mediated porcine coronary SMC relaxation. Coronary small arteries dissected from the apex of porcine hearts were mounted on wire myograph for Up 4 A concentration responses (10 -9 -10 -5 M). Up 4 A- mediated relaxation was significantly blunted in isolated porcine coronary small arteries without endothelium (Emax: 70 ± 5%) vs. arteries with intact endothelium (Emax: 93 ± 4%). Up 4 A-induced coronary SMC relaxation was attenuated by the A 2A receptor antagonist (SCH58261) (Emax: 24 ± 5%) but not the A 2B receptor antagonists (MRS1754, Emax: 80 ± 8%; CVT6883, Emax: 78 ± 9%) or the non-selective P2R antagonist (PPADS, Emax: 76 ± 10%). Despite more abundant endogenous A 2B receptor expression vs. A 2A receptors (~20-fold difference), Up 4 A affected neither A 2A nor A 2B receptor mRNA level, as assessed with real-time PCR, in primary cultured porcine SMCs. Up 4 A-induced coronary SMC relaxation was blunted by H 2 O 2 catabolism with catalase (Emax: 61 ± 10%). This effect was not altered by K ATP channel blockade glibenclamide (Emax: 75 ± 5%). Finally, SCH58261 (Emax: 18 ± 8%) attenuated Up 4 A- indcued porcine coronary SMC relaxation to the similar extent as the combination of SCH58261 and catalase (Emax: 20 ± 8%). In conclusion, Up 4 A-induced porcine coronary SMC relaxation is mediated by activation of A 2A -H 2 O 2 axis. This process does not involve A 2B receptors, P2 receptors or K ATP channels.