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。在本研究中，我们获得了以下结果.在人血管平滑肌细胞中，氧化低密度脂蛋白和氧化应激可诱导血红素氧合酶产生CO，并呈时间和剂量依赖性.在人内皮细胞中，高浓度的葡萄糖可刺激精氨酸的转运活性，增加NO的产生.在小鼠巨噬细胞中，氧化LDL可诱导血红素加氧酶的产生，而氧化LDL对精氨酸的转运活性无明显影响，NO的产生也不明显，提示在氧化应激条件下，氧化应激诱导的血红素加氧酶可增加CO的产生，而NO不产生。CO生成的调节可能不同于NO生成的调节。CO可能在氧化应激条件下起血管张力调节剂的作用，这与NO起作用的条件不同。1998年，由英国和日本政府支持的UK98艺术节将在日本举行。在本共同研究的过程中，我们同意作为UK98 Festival的活动之一，于1998年11月在筑波大学举办题为“氧化应激中抗氧化系统的调节”的研讨会。英国理事会为这次研讨会提供了财政支持。

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.