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Induction of Reperfusion Injury by Endothelium-derived Autacoids

内皮源性自体酸诱导再灌注损伤

基本信息

批准号：
08670061
负责人：
OKADA Takao
金额：
$ 1.15万
依托单位：
Juntendo University School of Medicine
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
1996
资助国家：
日本
起止时间：
1996 至 1997
项目状态：
已结题

项目摘要

There are complicated interactions between active oxygens and autacoids and the influences of these interactions on the heart are modified significantly by the various pathophysiological conditions. Superoxide anion (O_2^-) constrict coronary artery resulting in increased release of nitric oxide (NO). The increased NO interact with O_2^- to form peroxynitrite (ONOO^-) and damages heart. Thus, although NO is protective in the case of reoxygenation injury, it is harmful when there are enormous amount of O_2^-. High concentration of hydrogen peroxide (H_2O_2) damages heart. However, when low concentration of H_2O_2 is coexist with O_2^-, H_2O_2 inhibits the O_2^--induced vasoconstriction by increasing the release of PGI_2. Which suppresses the increase in NO release, formation of ONOO^- and irreversible myocardial injury. The influence of O_2^- persist even after it has been washed out.Under the control condition, neither administration of NO nor inhibition of NO synthesis affects the profile of prostanoids release. However, when NO was administered after the O_2^- perfusion, NO induced coronary vasoconstriction. This paradoxical vasoconstriction is caused by the NO-induced increase in vasoconstricting prostanoids, such as PGF_<2alpha> and TXA_2. Inhibition of prostanoid synthesis with indomethacin reversed the NO-induced vasoconstriction to vasorelaxation. The interaction between NO and PGI_2 was also altered after hypoxia. Under the control condition, it was suggested that NO is more important than PGI_2 on the regulation of vascular tone, because inhibition of NO caused vasoconstriction, and inhibition of PGI_2 induced increased NO release. However, after the hypoxia, inhibition of NO resulted in increased release of PGI_2, and conversely, inhibition of PGI_2 synthesis suppressed NO release indicating that under the pathophysiological condition, NO synthesis is regulated by PGI_2.

活性氧和自育素之间存在复杂的相互作用，这些相互作用对心脏的影响会因各种病理生理条件而显著改变。超氧阴离子（O_2^-）使冠状动脉收缩，导致一氧化氮（NO）释放增加。增加的NO与O_2^-相互作用形成过氧亚硝酸根（ONOO^-）而损害心脏。因此，尽管NO对复氧损伤具有保护作用，但当存在大量O_2^-时，NO是有害的。高浓度过氧化氢（H_2O_2）对心脏有损伤作用。当低浓度H_2O_2与O_2^-共存时，H_2O_2通过增加PGI_2的释放而抑制O_2^-引起的血管收缩。其抑制NO释放增加、ONOO^-形成和不可逆的心肌损伤。在对照条件下，无论是给予NO还是抑制NO的合成，都不影响前列腺素类化合物的释放。而在O_2 ~-灌注后再给予NO时，NO可引起冠状动脉收缩。这种反常的血管收缩是由NO诱导的收缩血管的前列腺素如PGF_2和TXA_2的增加引起<2alpha>的。用吲哚美辛抑制前列腺素合成可逆转NO引起的血管收缩为血管舒张。缺氧后NO与PGI_2的相互作用也发生改变。在对照条件下，NO比PGI_2对血管张力的调节更重要，因为抑制NO引起血管收缩，而抑制PGI_2则引起NO释放增加。缺氧后，NO的抑制导致PGI_2的释放增加，反之，PGI_2的合成抑制了NO的释放，说明在病理生理条件下，NO的合成受PGI_2的调节。