Ha. Olanrewaju et al., ROLE OF ENDOTHELIUM IN HYPERPOLARIZATION OF CORONARY SMOOTH-MUSCLE BYADENOSINE AND ITS ANALOGS, Journal of cardiovascular pharmacology, 25(2), 1995, pp. 234-239
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.