在不同环节阻断RAAS对肾血管高血压大鼠左室重构的影响

Effects of RAAS Blockade at Different Level on the Left Ventricular Remodeling in Renovascular Hypertension Rats

目的探讨在肾血管性高血压左室肥厚(LVH)形成过程中在不同环节阻断RAAS对肾血管性高血压大鼠心肌纤维化以及左室重构的影响。方法采用两肾一夹(2K1C)法在SD大鼠中建立肾血管性高血压模型,随机分为非药物干预组(N组)、阻断醛固酮受体组(螺内酯50mg·kg-1·d-1灌胃,S组)、阻断血管紧张素Ⅱ受体组(缬沙坦30mg·kg-1·d-1灌胃,V组)、阻断血管紧张素Ⅱ受体+阻断醛固酮受体组(螺内酯50mg·kg-1·d-1+缬沙坦30mg·kg-1·d-1灌胃,S+V组),并以假手术组大鼠(C组)为对照。采用心脏超声观察各组大鼠心脏结构和功能的变化;放射免疫法检测各组大鼠心肌组织中血管紧张素Ⅱ、醛固酮的浓度;Woessner法测定心肌组织中胶原浓度。结果用药8周后V组、S+V组的血压、左室收缩期径线室壁应力、舒张末期左室后壁厚度、相对室壁厚度以及左室重量指数等指标均明显低于N组及S组(P<0.05)。S组、V组、S+V组心肌组织中AngⅡ浓度、心肌胶原含量、心肌内血管周围胶原面积、胶原容积分数均明显低于H组(P<0.05)。结论(1)2K1C法可以在SD大鼠中产生明确的肾血管性高血压、LVH、心肌纤维化以及心功能减退。(2)应用缬沙坦阻断血管紧张素Ⅱ受体在降低血压的同时可以防止心肌纤维化以及LVH的形成,改善左室功能;

s Objective To investigate the effects of RAAS blockade at different level on the myocardial fibrosis and left ventricular remodeling during the development of left ventricular hypertrophy (LVH) in renovascular hypertension rats. Methods Two-kidney, one-clip (2K1C) renovascular hypertension was induced in Sprague-Dawley rats. The rats were randomized to non-intervention group (N group), aldosterone receptor blockade group (gorged spironolactone 50mg·kg-1·d-1, S group), angiotensinⅡ receptor blockade group (gorged valsartan 30mg·kg-1·d-1 V group) and angiotensinⅡ receptor plus aldosterone receptor blockade group (gorged spironolactone 50mg·kg-1·d-1 and valsartan 30mg·kg-1·d-1 at same time, S+V group). The sham-operated rats served as control group (C group). The changes of heart structure and function in all groups were observed with echocardiogram. The concentration of angiotensinⅡ (AngⅡ) and aldosterone (ALD) in left ventricle was assessed by radioimmunoassay. The Woessner's method was used to estimate the collagen content in left ventricle. Results After 8 weeks treatment, blood pressure, MESS, LVPWD, RWT and LVMI in V group and S+V group were decreased significantly compared with N group and S group (P<0.05). The collagen content, PVCA, CVF and the concentration of AngⅡ in S group, V group and S+V group were much lower than in N group (P<0.05). Conclusions (1) Renovascular hypertension, LVH, myocardial fibrosis and left ventricular dysfunction can be developed in 2K1C rats. (2) Blockade angiotensinⅡ receptor using valsartan is very effective in controlling blood pressure, reducing myocardial fibrosis and suppressing LVH in renovascular hypertension rats. Blockade aldosterone receptor using spironolactone can reduce myocardial fibrosis, but has weak effects on blood pressure and suppressing LVH.