NITRIC-OXIDE (EDRF) ENHANCES THE VASORELAXING EFFECT OF DIHYDROPYRIDINE CALCIUM-ANTAGONISTS IN ISOLATED HUMAN MIDDLE CEREBRAL-ARTERIES

Experiments were performed on perfused human middle cerebral artery (M CA) precontracted with prostaglandin F2(alpha). Nifedipine, isradipine and lacidipine induced dose-dependent relaxant effects on MCA segment s. Effects of nifedipine were rather similar on MCA segments with and without endothelium; however, responses of endothelium-denuded vessel segments to isradipine and especially lacidipine were lower than those of vessels with the intact endothelium. The vasodilator effects of th ese agents, especially isradipine and lacidipine, on vessel segments w ith intact endothelium in the presence of a NO-synthase inhibitor, N-n itro-L-arginine, were significantly attenuated whereas a cycloxygenase inhibitor, indomethacin, did not significantly alter vasodilator resp onses of MCA segments to all calcium antagonists tested. It is suggest ed that the endothelium modulates vascular relaxation to dihydropyridi nes by an enhancement of calcium antagonist actions by basally release d EDRF/NO at the level of vascular smooth muscles or by a dihydropyrid ine-induced increase in the release of EDRF/No.