Wu R, Millette E, Wu L, de Champlain J
Department of Physiology, Faculty of Medicine, University of Montreal, Quebec, Canada.
J Hypertens. 2001 Apr;19(4):741-8. doi: 10.1097/00004872-200104000-00011.
To investigate the basal and NADH-stimulated superoxide (.O2-) production and inactivation by Cu/Zn superoxide dismutase (SOD) in aorta from spontaneously hypertensive rats (SHR) and from desoxycorticosterone acetate (DOCA)-salt hypertensive (DOCA-HT) rats.
Tissue .O2- levels were estimated with the lucigenin-enhanced chemiluminescence method in aorta and cultured smooth muscle cells (SMCs) from SHR and in aorta from DOCA-HT rats treated for 4 weeks.
The basal aortic .O2- generation was increased by 135 and 100%, and the NADH stimulated .O2- production was also increased 37 and 22% in SHR and in DOCA-HT rats compared to their normotensive controls, respectively. Although no difference existed in blood pressure as well as in basal and in NADH stimulated .O2- production between Wistar-Kyoto (WKY) rats and SHR rats at age of 6 weeks, O2- production and blood pressure increased concomitantly in SHR aged 9 and 12 weeks. Basal and NADH-stimulated .O2- production, in cultured SMCs, was also 80 and 64% higher, respectively, in SHR compared to WKY rats. The NADH oxidase activity was found to be increased in aorta from both SHR and DOCA-HT rats but SOD activity was reduced only in aorta from DOCA-HT rats.
An enhanced .O2- formation resulting from an increased NADH oxidase activity was found in aorta from SHR and DOCA-HT rats. Cultured arterial SMCs from SHR also generated excessive .O2- formation under basal and stimulated conditions. The age-related increase in vascular .O2- formation in association with the rise in blood pressure in SHR suggests that the oxidative stress might contribute to the development of hypertension. NADH oxidase activity was greater in aorta of both hypertension models, but a decrease of Cu/Zn SOD activity could also contribute to the high level of aortic .O2- in DOCA-HT rats.
研究自发性高血压大鼠（SHR）和醋酸脱氧皮质酮（DOCA）-盐性高血压（DOCA-HT）大鼠主动脉中基础状态及烟酰胺腺嘌呤二核苷酸（NADH）刺激下超氧阴离子（.O2-）的产生情况以及铜/锌超氧化物歧化酶（SOD）对其的灭活作用。
采用光泽精增强化学发光法测定SHR主动脉及培养的平滑肌细胞（SMC）以及经4周治疗的DOCA-HT大鼠主动脉中的组织.O2-水平。
与正常血压对照组相比，SHR和DOCA-HT大鼠的基础主动脉.O2-生成分别增加了135%和100%，NADH刺激的.O2-产生也分别增加了37%和22%。尽管6周龄的Wistar-Kyoto（WKY）大鼠和SHR大鼠在血压以及基础状态和NADH刺激的.O2-产生方面没有差异，但9周龄和12周龄的SHR大鼠的.O2-产生和血压同时升高。与WKY大鼠相比，SHR培养的SMC中基础状态和NADH刺激的.O2-产生也分别高出80%和64%。发现SHR和DOCA-HT大鼠主动脉中的NADH氧化酶活性均增加，但仅DOCA-HT大鼠主动脉中的SOD活性降低。
在SHR和DOCA-HT大鼠的主动脉中发现，由于NADH氧化酶活性增加导致.O2-生成增强。SHR培养的动脉SMC在基础状态和刺激条件下也产生过多的.O2-。SHR中与血压升高相关的血管.O2-生成随年龄增长而增加，这表明氧化应激可能有助于高血压的发展。两种高血压模型的主动脉中NADH氧化酶活性均较高，但铜/锌SOD活性降低也可能导致DOCA-HT大鼠主动脉中.O2-水平升高。
