ROLE OF ENDOTHELIUM IN HYPERPOLARIZATION OF CORONARY SMOOTH-MUSCLE BYADENOSINE AND ITS ANALOGS

We studied the effects of adenosine (AD) and its analogues, 5'-N-ethyl carboxamidoadenosine (NECA) and 2-chloroadenosine (CAD) on membrane po tential of porcine coronary artery with an without endothelium, conduc ting experiments with addition of indomethacin (10(-5)M) to rule out i nvolvement of prostanoids. Average resting membrane potential (RMP) in porcine coronary artery was -51.1 +/- 0.2 and -50.3 +/- 0.2 mV, with and without endothelium, respectively. AD agonists at 10(-5)M caused a significant increase in RMP to -69.5 +/- 0.2 mV for AD, to -82.2 +/- 0.3 mV for CAD, and to -81.2 +/- 0.3 mV for NECA in porcine coronary a rteries with intact endothelium. Moreover, AD agonists at 10(-5)M caus ed a smaller but significant increase in RMP to -54.3 +/- 0.2 mV for A D, -56.1 +/- 0.1 mV for CAD, and -61.1 +/- 0.2 mV for NECA without end othelium. The average RMP for human coronary artery with and without e ndothelium was -66.1 +/- 0.5 and -64.0 +/- 0.4, respectively. Qualitat ively, similar effects of AD and its analogues were observed in two hu man coronary arteries. The AD receptor antagonist, 8-sulfophenyltheoph ylline (8-SPT, 10(-5)M) blocked hyperpolarization caused by AD and its analogues with and without endothelium both in porcine and human coro nary arteries. The hyperpolarization caused by CAD and NECA in porcine coronary artery was attenuated in part by the nitric oxide (NO) synth ase inhibitors N-monomethyl-L-arginine (L-NMMA, 10(-5)M) and N-nitro-L -arginine methylester (L-NAME, 10(-5)M), and the effect of L-NAME was reversed by L-arginine (L-ARG, 10(-4)M). These results suggest that hy perpolarization of human and porcine coronary arteries by AD and its a nalogues is at least partly endothelium dependent and may involve NO r elease.