Endothelium-dependent relaxation to hydrogen peroxide in canine basilar artery: A potential new cerebral dilator mechanism

In prostglandin F-2 alpha(PGF(2 alpha))-precontracted isolated canine basil ar arterial rings, hydrogen peroxide (H2O2) produced endothelium-dependent relaxations at concentrations of from 4.4 x 10(-7) - similar to 4.4 x 10(-5 ) M. Removal of extracellular Ca2+ ([Ca2+](o)) attenuated the relaxant effe cts of H2O2. Complete inhibition of H2O2 relaxant action was obtained after buffering intracellular Ca2+ ([Ca2+](i)), in the endothelial cells, with 1 0 mu M 1,2-bis (2-aminophenoxy) ethane-N,N,N',N'-tetraacetic acid (BAPTA-AM ). The H2O2-induced relaxations could be abolished completely by 1200 u/ml catalase and was suppressed significantly by 0.5 mu M atropine, 150 mu M N- G-monomethyl-arginine (L-NMMA), 50 mu M N-G-nitro-L-arginine methyl ester ( L-NAME), 1 mu M Fe2+, or 5 mu M methylene blue. These inhibitory effects of L-NMMA, L-NAME, or atropine could be reversed partly by 50 mu M L-arginine . The Fe2+ inhibition of H2O2-stimulated relaxation was reduced significant ly by either 1 mM deferoxamine (a Fe2+ chelator) or 100 mu M dimethyl sulfo xide (DMSO, a (OH)-O-. scavenger). Such relaxant effects of H2O2 were enhan ced, significantly, by an acetylcholinesterase antagonist, neostigmine. A v ariety of pharmacological antagonists (of diverse vasodilator agents) could not inhibit the relaxant action of H2O2. Our observations suggest that at suitable pathophysiological concentrations, H2O2 could induce release of an endothelium-derived relaxing factor (EDRF), probably nitric oxide (NO), fr om endothelial cells of the canine cerebral artery. The H2O2 relaxant effec ts are clearly Ca2+-dependent, require formation of cyclic guanosine monoph osphate (cGMP), and may be associated with release of endogenous acetylchol ine (ACh). (C) 1998 Elsevier Science Inc.