一氧化氮中介雷米普利拉对氧自由基损伤兔胸主动脉内皮的保护作用

Nitric oxide mediates the protective effect of ramiprilatagainst damages of rabbit aortic endothelium byoxygen free radicalsi

采用离体兔胸主动脉淋浴灌注方法，探讨雷米普利拉（Ｒａｍ）对氧自由基损伤血管内皮功能的保护作用及其机理．结果发现，电解Ｋｒｅｂｓ液产生的氧自由基明显抑制血管内皮依赖性舒张，降低血管壁氧化氮（ＮＯ）和ｃＧＭＰ含量，并使丙二醛含量增加；Ｒａｍ消除电解所致的上述作用，并呈现剂量依赖性；ＮＯ合成的前体物质─—Ｌ－精氨酸亦具有相似的保护作用；Ｒａｍ和Ｌ－精氨酸的保护作用均可被ＮＯ合成酶抑制剂所阻断。这些结果提示，Ｒａｍ抗氧自由基损伤血管内皮的作用可能与其促进内皮细胞合成，释放ＮＯ有关。Ｐ＜０．０１，ｃｏｍｐａｒｅｄｗｉｔｈｃｏｎｔｒｏｌ．Ｐ＜０．０５，Ｐ＜０．０１．ｃｏｍｐａｒｅｄｗｉｔｈＥｌｅ；Ｐ＜０．０１．ｃｏｍｐａｒｅｄｗｉｔｈＲａｍΔΔＰ＜０．０１．ｃｏｍｐａｒｅｄｗｉｔｈＬ－Ａｒｇ．ＳｉｍｉｌａｒｒｅｓｕｌｔｗａｓｏｂｔａｉｎｅｄｉｎｔｈｅｔｉｓｓｕｅｔｒｅａｔｅｄｗｉｔｈＬ－Ａｒｇ．Ｈｏｗｅｖｅｒ．ｔｈｅｅｆｆｅｃｔｏｆＲａｎｉｏｒＬＡｒｇｗａｓａｂｒｏｇａｔｃｄｉｎｔｈｅｐｒｅｓｅｎｃｅｏｆＮＡｒｇ．Ｒｅｄｕｃｔｉｏｎｂｙｅｌｅｃｔｒｏｌｙｓｉｓｏｆｎｉｔｒｉｔｅｖａｌｕｅｗａｓｎｏｔｉｎｆｌｕｅｎｃｅｄ?

Ramiprilat (Ram) was shown to pro-tect against damages induced by oxygen free radicalson aortic endothelium. The aim of the present studywas to investigate whether this protection of Ram ismediated by the facilitation of release of nitnc oxide.The superfusion cascade bioassay of rabbit thoracicaorta was used. Oxygen free radicals were generated byelectrolysis of Krebs solution. The content of cyclicguanylic acid (cGMP), inorganic nitnte, andmalondialdehyde (MDA) in the donor vessel was as-sayed biochemically. Oxygen free radicals generated inelectrolytic Krebs solution caused inhibition ofvasodilator responses of rabbit thoracic aorta toaeetylcholine (ACh), decrease in levels of cGMP andinorganic nitrite as well as elevation of MDA contentin the rabbit aortic segment. The protective effect ofRam on ACh-relaxation was concentration-depen-dent. L-Arginine also significantly prevented damagesinduced by free mdicals. The protective effects of Ramand L-arginine were abrogated by treatment withnitro-L-arginine (30 μmol · L-1 ), while indometacin(10 μmol · L-1 ) did not prevented the protective effectof Ram on vasodilator responses to ACh. The presentstudy suggests that Ram could protect rabbit aorticendothelium against damages induced by oxygen freeradicals, and that the effect of Ram may be due tofacilitation of the release of nitric oxide resulting in re-duction of lipid peroxidation.