Yang Z W, Zhang A, Altura B T, Altura B M
Department of Physiology, State University of New York, Health Science Center at Brooklyn, 11203, USA.
Brain Res Bull. 1998 Oct;47(3):257-63. doi: 10.1016/s0361-9230(98)00120-8.
In prostglandin F2alpha(PGF2alpha)-precontracted isolated canine basilar arterial rings, hydrogen peroxide (H2O2) produced endothelium-dependent relaxations at concentrations of from 4.4 x 10(-7) - approximately 4.4 x 10(-5) M. Removal of extracellular Ca2+ ([Ca2+]0) attenuated the relaxant effects of H2O2. Complete inhibition of H2O2 relaxant action was obtained after buffering intracellular Ca2+ ([Ca2+]i), in the endothelial cells, with 10 microM 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 microM atropine, 150 microM NG-monomethyl-arginine (L-NMMA), 50 microM NG-nitro-L-arginine methyl ester (L-NAME), 1 microM Fe2+, or 5 microM methylene blue. These inhibitory effects of L-NMMA, L-NAME, or atropine could be reversed partly by 50 microM L-arginine. The Fe2+ inhibition of H2O2-stimulated relaxation was reduced significantly by either 1 mM deferoxamine (a Fe2+ chelator) or 100 microM dimethyl sulfoxide (DMSO, a *OH scavenger). Such relaxant effects of H2O2 were enhanced, significantly, by an acetylcholinesterase antagonist, neostigmine. A variety 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), from endothelial cells of the canine cerebral artery. The H2O2 relaxant effects are clearly Ca2+-dependent, require formation of cyclic guanosine monophosphate (cGMP), and may be associated with release of endogenous acetylcholine (ACh).
在前列腺素F2α（PGF2α）预收缩的离体犬基底动脉环中，过氧化氢（H2O2）在浓度为4.4×10（-7）至约4.4×10（-5）M时产生内皮依赖性舒张。去除细胞外Ca2 +（[Ca2 +] 0）减弱了H2O2的舒张作用。用10 microM 1,2-双（2-氨基苯氧基）乙烷-N，N，N'，N'-四乙酸（BAPTA-AM）缓冲内皮细胞内的Ca2 +（[Ca2 +] i）后，H2O2的舒张作用完全被抑制。H2O2诱导的舒张作用可被1200 u/ml过氧化氢酶完全消除，并被0.5 microM阿托品、150 microM NG-单甲基精氨酸（L-NMMA）、50 microM NG-硝基-L-精氨酸甲酯（L-NAME）、1 microM Fe2 +或5 microM亚甲蓝显著抑制。L-NMMA、L-NAME或阿托品的这些抑制作用可被50 microM L-精氨酸部分逆转。1 mM去铁胺（一种Fe2 +螯合剂）或100 microM二甲基亚砜（DMSO，一种*OH清除剂）均可显著降低Fe2 +对H2O2刺激的舒张作用的抑制。乙酰胆碱酯酶拮抗剂新斯的明可显著增强H2O2的这种舒张作用。多种（不同血管舒张剂的）药理学拮抗剂均不能抑制H2O2的舒张作用。我们的观察结果表明，在合适的病理生理浓度下，H2O2可诱导犬脑动脉内皮细胞释放内皮源性舒张因子（EDRF），可能是一氧化氮（NO）。H2O2的舒张作用明显依赖于Ca2 +，需要环磷酸鸟苷（cGMP）的形成，并且可能与内源性乙酰胆碱（ACh）的释放有关。
