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从受体水平阻断肾素- 血管紧张素系统的生物学效应来探讨血管紧张素Ⅱ和醛固酮对高血压大鼠心肌肥厚及纤维化的作用,将二肾一夹型高血压大鼠分为高血压治疗组和高血压对照组,高血压治疗组在术后第16 周通过饮水给予缬沙坦(10 μgg·d),高血压对照组和假手术组不给药。术后第16 周、20 周及28 周分别处死大鼠,测定血压、心脏和左心室重量、血浆和心肌血管紧张素Ⅱ及醛固酮浓度、左心室重量指数、心肌胶原含量及胶原容积分数。结果发现,高血压对照组大鼠血浆和心肌血管紧张素Ⅱ及醛固酮浓度、左心室重量指数、心肌胶原浓度及胶原容积分数均显著高于假手术组( P<0.05 或0.005);与高血压对照组比较,高血压治疗组血浆血管紧张素Ⅱ浓度明显增高,血压、左心室重量指数、血浆醛固酮浓度、心肌胶原浓度及胶原容积分数则显著降低(P<0.05) ,且主要是Ⅰ型胶原减少。结果提示,肾血管性高血压大鼠左心室重塑与心肌血管紧张素Ⅱ和醛固酮浓度密切相关,血管紧张素Ⅱ1 型受体拮抗剂缬沙坦可以阻断血管紧张素Ⅱ的病理生理作用,抑制醛固酮的释放,逆转左心室重塑,心脏局部血管紧张素Ⅱ的生物学效应可能主要是血管紧张素Ⅱ1 型受体所介导
To investigate the effect of angiotensin Ⅱ and aldosterone on cardiac hypertrophy and fibrosis in hypertensive rats by blocking the biological effect of renin-angiotensin system at receptor level, and to divide the two-kidney one-clip hypertensive rats into Hypertension treatment group and hypertension control group, hypertension treatment group were given valsartan (10 μg g · d) by drinking water at 16 weeks after operation. Hypertension control group and sham operation group were not given. The rats were sacrificed at the 16th week, the 20th week and the 28th week after operation. Blood pressure, heart and left ventricular weight, plasma and myocardial angiotensin II and aldosterone concentrations, left ventricular mass index, myocardial collagen content and collagen volume fraction were measured. The results showed that plasma and myocardial concentrations of angiotensin Ⅱ and aldosterone, left ventricular mass index, myocardial collagen concentration and collagen volume fraction in hypertensive control group were significantly higher than those in sham operation group (P <0.05 or 0.005) ; Compared with the control group, the concentration of plasma angiotensin Ⅱ in hypertension group was significantly higher than that in the control group (P <0.05). The blood pressure, left ventricular mass index, plasma aldosterone concentration, myocardial collagen concentration and collagen volume fraction were significantly decreased And mainly type Ⅰ collagen decreased. The results suggest that left ventricular remodeling in renovascular hypertensive rats is closely related to myocardial angiotensin Ⅱ and aldosterone concentrations. Angiotensin Ⅱ type 1 receptor antagonist valsartan can block the pathophysiological effects of angiotensin Ⅱ, Inhibition of aldosterone release, reverse left ventricular remodeling, the biological effects of local cardiac angiotensin Ⅱ may be mainly mediated by angiotensin Ⅱ type 1 receptor