Regulation by Oxidative Stress of CO-and NO-Mediated Signal Transduction in Vascular Cells

一氧化碳（CO）和一氧化氮（NO）在血管张力的生理调节和动脉粥样硬化的发病机制中起重要作用。在目前的研究中，我们得到了以下结果。在人血管平滑肌细胞中，氧化LDL和氧化应激诱导生成一氧化碳的血红素加氧酶的活性呈时间和剂量依赖性。在人内皮细胞中，高浓度葡萄糖培养可刺激精氨酸的转运活性，增加一氧化氮的产生。在小鼠巨噬细胞中，氧化LDL诱导血红素加氧酶。然而，精氨酸的运输活性保持不变，氧化LDL无法检测到NO的产生。综上所述，在氧化应激条件下，氧化应激诱导的血红素加氧酶增加了CO的产生，而不产生NO。CO产生的调控可能与NO产生的调控不同。在不同于NO的氧化应激条件下，CO可能作为血管张力的调节剂。包含这些结果的手稿正在准备论文。1998年，由英国和日本政府支持的UK98音乐节将在日本举行。在目前的联合研究过程中，我们同意于1998年11月在筑波大学举行题为“氧化应激中抗氧化系统的调节”的研讨会，作为UK98节的活动之一。英国文化协会为本次研讨会提供了资金支持。

Carbon monoxide (CO) and nitric monoxide (NO) play an important role in the physiological regulation of vascular tone and pathogenesis of atherosclerosis. In the present study we have obtained the following results.1. In human vascular smooth muscle cells, the activity of heme oxygenase, which generates CO,was induced by oxidized LDL and oxidative stress in a time-and dose-dependent manner.2. In human endothelial cells, the transport activity of arginine was stimulated and the production of NO increased by culturing the cells in higher concentration of glucose.3. In mouse macrophages, heme oxygenase was induced by oxidized LDL.However, the transport activity of arginine remained unchanged and production of NO was undetectable by oxidized LDL.From these results, it is suggested that under oxidative stress conditions heme oxygenase induced by oxidative stress increases the production of CO whereas NO is not generated. It is likely that the regulation of CO production is different from that of NO production. CO may function as the modulator of vascular tone under the oxidative stress conditions which are different from those where NO functions. Manuscripts containing these results are in preparation for papers.In 1998 UK98 Festival supported by the governments of UK and Japan will be held in Japan. In the course of the present joint research, we agreed as one of the events of UK98 Festival to hold a symposium entitled "Regulation of antioxidant system in oxidative stress" at University of Tsukuba, November l998. The British Council has offered a financial support for this symposium.