Activation of adenosine A(2A) but not A(2B) receptors is involved in uridine adenosine tetraphosphate-induced porcine coronary smooth muscle relaxation

Activation of both adenosine A(2A) and A(2B) receptors (A(2B)R) 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)R in smooth muscle cells (SMC). We further investigated whether activation of A(2B)R is involved in Up(4)A-mediated coronary SMC 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 effect. Coronary small arteries dissected from the apex of porcine hearts were mounted on wire myograph for Up(4)A concentration responses. Up(4)A-induced coronary SMC relaxation was attenuated by A(2A)R but not A(2B)R antagonism or non-selective P2R antagonism, despite greater endogenous A(2B)R expression vs. A(2A)R in both coronary small arteries and primary cultured coronary SMCs. Moreover, Up(4)A-induced coronary SMC relaxation was blunted by H(2)O(2) catabolism. This effect was not altered by K(ATP) channel blockade. Combination of H(2)O(2) catabolism and A(2A)R antagonism attenuated Up(4)A-induced coronary SMC relaxation to the similar extent as A(2A)R antagonism alone. Collectively, Up(4)A-induced porcine coronary SMC relaxation is mediated by activation of A(2A)R-H(2)O(2) pathway. This process does not involve A(2B)R, P2R or K(ATP) channels.