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 (MCA) precontracted with prostaglandin F2a. Nifedipine, isradipine and lacidipine induced dose-dependent relaxant effects on MCA segments. 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 intact endothelium. The vasodilator effects of these agents, especially isradipine and lacidipine, on vessel segments with intact endothelium in the presence of a NO-synthase inhibitor, N-nitro-L-arginine, were significantly attenuated whereas a cyclooxygenase inhibitor, indomethacin, did not significantly alter vasodilator responses of MCA segments to all calcium antagonists tested. It is suggested that the endothelium modulates vascular relaxation to dihydropyridines by an enhancement of calcium antagonist actions by basally released EDRF/NO at the level of vascular smooth muscles or by a dihydropyridine-induced increase in the release of EDRF/NO.
Akopov
S E
SE
Department of Pharmacology, Yerevan Medical Institute, Armenia.
D000328:Adult; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D002536:Cerebral Arteries / Q000187:drug effects / Q000378:metabolism; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D004095:Dihydropyridines / Q000494:pharmacology; D015237:Dinoprost / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006801:Humans; D066298:In Vitro Techniques; D007213:Indomethacin / Q000494:pharmacology; D017275:Isradipine / Q000494:pharmacology; D009126:Muscle Relaxation / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D009543:Nifedipine / Q000494:pharmacology; D009569:Nitric Oxide / Q000378:metabolism*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D019335:Nitroarginine; D014665:Vasodilator Agents / Q000494:pharmacology*
D002121:Calcium Channel Blockers; D016861:Cyclooxygenase Inhibitors; D004095:Dihydropyridines; D004791:Enzyme Inhibitors; D014665:Vasodilator Agents; D019335:Nitroarginine; C060285:lacidipine; D009569:Nitric Oxide; D001120:Arginine; D015237:Dinoprost; D019001:Nitric Oxide Synthase; D009543:Nifedipine; D007213:Indomethacin; D017275:Isradipine