诱导型一氧化氮合酶的激活与血压的关系

谭敦勇　 程少冰　 陈小琳　 张穗梅　 杨皓庄　 彭旭　 唐朝枢　 张超　 孟宪璋　

摘　要：本实验旨在探讨诱导型一氧化氮合酶(iNOS)的激活与血压之间的关系。三组SD大鼠分别静脉输注不同浓度(0.3％,4％及8%)NaCl溶液以使其处于不同的血压水平。运用同位素标记的L-精氨酸转换成L－Citrulline的转换率变化及Greiss反应,分别测定不同血压时iNOS的活性及NO的生成量。另四组大鼠包括正常Wistar、正常SD、高盐诱导的高血压(NaHR)及自发性高血压大鼠(SHR),经测定血压后,取主动脉血管并以Western印迹杂交法测定其iNOS蛋白水平。结果表明,血压较低时,SD大鼠iNOS活性基本没有改变,而在输入4％及8％NaCl并处于较高血压水平的SD大鼠,其iNOS活性及NO生成均明显升高。此外Western印迹表明,两种高血压大鼠主动脉组织iNOS蛋白水平均较正常Wistar及正常SD大鼠高,密度扫描表明,NaHR及SHR主动脉组织iNOS蛋白分别较正常SD大鼠及正常Wistar大鼠升高149％及261％。这一结果提示,诱导型一氧化氮合酶是血液动力学调控的重要组成部分,尤其是在血压处于较高水平时,iNOS具有重要的代偿调节作用。除细胞因子、细菌产物等之外,血压也是调节iNOS表达及活性的重要因素之一。
关键词：一氧化氮;诱导型一氧化氮合酶;动脉血压
分类号：Q463; R544　文献标识码：A

Involvement of pressure-related mechanism in activation of inducible nitric oxide synthase

TAN Dun-Yong（Department of Pathophysology, Jinan University Medical College, Guangzhou 510632）　
TAN Dun-Yong（First Affiliated Hospital, Beijing University, Beijing 100032）　
CHENG Shao-Bing（Department of Pathophysology, Jinan University Medical College, Guangzhou 510632）　
CHEN Xiao-Lin（Department of Pathophysology, Jinan University Medical College, Guangzhou 510632）　
ZHANG Sui-Mei（Department of Pathophysology, Jinan University Medical College, Guangzhou 510632）　
YANG Hao-Zhuang（Department of Pathophysology, Jinan University Medical College, Guangzhou 510632）　
PENG Xu（First Affiliated Hospital, Beijing University, Beijing 100032）　
TANG Chao-Shu（First Affiliated Hospital, Beijing University, Beijing 100032）　
ZHANG Chao（Department of Pathophysology, Jinan University Medical College, Guangzhou 510632）　
MENG Xian-Zhang（Department of Pathophysology, Jinan University Medical College, Guangzhou 510632）　

Abstract：The goal of this study was to clarify the relationship between blood pressure and inducible nitric oxide synthase (iNOS) activity. Different levels of blood pressure were obtained by long-term (six days) intravenous infusion of different concentrations (0.3%～8%) of NaCl solution to normal SD rats. iNOS activity assay and measurement of urinary nitrate/nitrite (UNOx), an index of NO production of the whole body, were carried out by isotope-labeled L-arginine convertion rate measurement and Greiss Reaction respectively. Groups of normotensive and hypertensive rats including normal Wistar rats, normal Sprague-Dawley (SD) rats, high NaCl-induced hypertensive rats (NaHR) and spontaneously hypertensive rats (SHR) were used to detect the changes in iNOS protein under normotension and hypertension by Western blotting. iNOS activity of aorta and kidney tissues and UNOx increased more significantly in hypertensive animals than in the normotensive control ones. Accordingly, iNOS protein in the aortas of NaHR and SHR increased by 149% and 261% respectively. It is suggested that in addition to cytokine and bacterial products etc, blood pressure is also an effective regulatory factor involved in iNOS activation and expression.
Keywords：nitric oxide; inducible nitric oxide synthase; arterial pressure

基金项目：This work was supported by The National Natural Science Foundation of China (No.39870359), Guangdong Provincial Natural Science Foundation of China (No.990958) and the Project Sponsored by SRF for ROCS, SEM.
作者单位：谭敦勇（暨南大学医学院病理生理教研室, 广州 510632）　
　　　　　谭敦勇（北京大学医学部第一医院, 北京 100032）　
　　　　　程少冰（暨南大学医学院病理生理教研室, 广州 510632）　
　　　　　陈小琳（暨南大学医学院病理生理教研室, 广州 510632）　
　　　　　张穗梅（暨南大学医学院病理生理教研室, 广州 510632）　
　　　　　杨皓庄（暨南大学医学院病理生理教研室, 广州 510632）　
　　　　　彭旭（北京大学医学部第一医院, 北京 100032）　
　　　　　唐朝枢（北京大学医学部第一医院, 北京 100032）　
　　　　　张超（暨南大学医学院病理生理教研室, 广州 510632）　
　　　　　孟宪璋（暨南大学医学院病理生理教研室, 广州 510632）　

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收稿日期：2000年7月9日

修稿日期：2000年11月16日