血管紧张素Ⅱ在内皮素诱导的大鼠高血压中的作用

目的探讨血管紧张素Ⅱ在内皮素-1诱导的大鼠高血压中的作用。方法 5～6周雄性SD大鼠随机分为3组:①对照组(1%氯化钠慢性灌注,n=7);②内皮素-1慢性灌注组2.5pmol/(kg.min),n=7];③内皮素-1+奥美沙坦治疗组(0.01%食物中混入,n=7)。Western blotting检测血浆血管紧张素原和主动脉ACE与AT1受体表达。放射免疫法检测血浆肾素活性、血管紧张素Ⅰ和血管紧张素Ⅱ水平。结果与对照组相比,内皮素-1慢性灌注组大鼠血压明显升高(121±2)vs(141±2)mmHg,P<0.05)],血浆肾素活性明显增加(3.1±0.6)vs(8.1±0.8)AngI/(mL.h),P<0.05)],血管紧张素Ⅰ(45±8)vs(122±28)fmol/mL]及血管紧张素Ⅱ水平(47±7)vs(94±13)fmol/mL]水平明显升高(P<0.05)。内皮素-1灌注未影响大鼠血浆血管紧张素原以及主动脉ACE和AT1受体表达。AT1受体拮抗剂奥美沙坦降低了内皮素-1慢性灌注引起的大鼠高血压。结论内皮素-1诱导的大鼠高血压与血管紧张素Ⅱ水平增高相关。内皮素-1与血管紧张素Ⅱ共同作用,促进了内皮素-1慢性灌注诱导的大鼠高血压进展。

Role of angiotensin II on endothelin-1 induced hypertension of rats

Objective To determine the role of angiotensin II in endothelin-1 induced hypertension of rats.Methods Male Sprague-Dawley rats were randomly treated with one of the following combinations for 2 weeks:①Control group:chronic 1%NaCl infusion(n=7),②Chronic endothelin-1 infusion2.5 pmol/(kg·min),n=7],③Endothelin-1 + olmesartan(0.01% in chow,n=7).Plasma AGT protein levels,ACE and AT1 receptor protein expression in aortic tissues were determined by western blotting analysis.PRA,angiotensin I and angiotensin II levels were measured by radioimmunoassays.Results Compared with control group,chronic endothelin-1 infused rats increased systolic blood pressure(121±2)vs(141±2)mmHg,P<0.05.Endothelin-1 infused rats showed higher plasma renin activity(8.1±0.8)AngI/(mL·h)],and angiotensin I(122±28)fmol/mL]and angiotensin II levels(94±13)fmol/mL]than 0.9% NaCl infused rats(3.1±0.6)AngI/(mL·h),(45±8)and(47±7)fmol/mL respectively](P<0.05).Plasma AGT protein levels,ACE and AT1 receptor protein expression in aortic tissues were similar between vehicle and Endothelin-1 infused rats.The Endothelin-1 induced hypertension was prevented by simultaneous treatment with olmesartan.Conclusion Endothelin-1 dependent hypertension is associated with augmentation of the angiotensin II level.The combined effects of the elevations in circulating endothelin-1 and angiotensin II may contribute to the development of hypertension induced by chronic endothelin-1 infusion.