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

We studied the effects of adenosine (AD) and its analogues, 5'-N-ethylcarboxamidoadenosine (NECA) and 2-chloroadenosine (CAD) on membrane potential of porcine coronary artery with an without endothelium, conducting experiments with addition of indomethacin (10(-5)M) to rule out involvement 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 arteries with intact endothelium. Moreover, AD agonists at 10(-5)M caused a smaller but significant increase in RMP to -54.3 +/- 0.2 mV for AD, -56.1 +/- 0.1 mV for CAD, and -61.1 +/- 0.2 mV for NECA without endothelium. The average RMP for human coronary artery with and without endothelium was -66.1 +/- 0.5 and -64.0 +/- 0.4, respectively. Qualitatively, similar effects of AD and its analogues were observed in two human coronary arteries. The AD receptor antagonist, 8-sulfophenyltheophylline (8-SPT, 10(-5)M) blocked hyperpolarization caused by AD and its analogues with and without endothelium both in porcine and human coronary arteries. The hyperpolarization caused by CAD and NECA in porcine coronary artery was attenuated in part by the nitric oxide (NO) synthase 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 hyperpolarization of human and porcine coronary arteries by AD and its analogues is at least partly endothelium dependent and may involve NO release.