诱导型一氧化氮合酶的激活与血压的关系

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印迹印交法测定其iNOS蛋白水平,结果表明,血压较低时,SD大鼠iNOS活基本没有改变,而在输入4％和8％NaCl并处于较高血压水平的SD大鼠,其iNOS活性及NO生存均明显升高,。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。

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

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 conversion 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.