血管紧张素Ⅱ1型受体拮抗剂与醛固酮受体拮抗剂对逆转高血压大鼠心肌重塑的作用

Effects of Angiotensin Ⅱ 1 Type Receptor Antagonist and Aldosterone Receptor Antagonist Reverse Myocardial Remodeling on Hypertensive Rats

在受体水平阻断肾素—血管紧张素系统 ,比较血管紧张素Ⅱ 1型受体拮抗剂与醛固酮受体拮抗剂对逆转高血压心肌重塑的作用 ,来探讨高血压性心肌重塑的可能机理。为此 ,制作二肾一夹型高血压大鼠模型形成心肌肥厚及纤维化 ,然后分成高血压对照组、缬沙坦组 [10 μg (kg·d) ]和螺内酯组 [4 0mg (kg·d) ]。分别观察给药前、给药后 4周和 12周血浆及心肌血管紧张素Ⅱ和醛固酮含量、左心室重量指数、心肌胶原含量、心肌胶原容积分数及Ⅰ、Ⅲ型胶原的病理特征。结果发现 ,与高血压对照组比较 ,缬沙坦组左心室重量指数、心肌胶原含量和心肌胶原容积分数显著下降 (P <0 .0 5 ) ,以降低Ⅰ型胶原沉积为主 ;螺内酯组左心室重量指数、心肌胶原含量和心肌胶原容积分数亦有所下降 (P <0 .0 5 ) ,以降低Ⅲ型胶原沉积为主 ,但作用不如缬沙坦。结果提示 ,左心室肥厚发展过程与心肌纤维化存在异时性。血管紧张素Ⅱ和醛固酮在心肌重塑过程中起关键作用 ,血管紧张素Ⅱ 1型受体可能主要介导Ⅰ型胶原的沉积 ,而醛固酮受体可能主要介导Ⅲ型胶原的沉积。

Aim To investigate the role of angiotensin Ⅱ(AngⅡ) 1 type recepter antagonist and aldosterone (Ald) receptor antagonist in reversing myocardial remodeling in hypertensive rats by blocking renin angiotensin system at receptor level and the mechanism of hypertensive myocordial remodeling. Methods Thirty nine male Wistar rats were devided into the shamo operated group, the hypertension group, the valsartan group [10 μg/(kg·d)] and spironolactone group [40 mg/(kg·d)]. Systolic blood pressure (SBP), left ventricular weight index (LVWI), plasma and myocardial AngⅡ/Ald concentration, myocardial collagen concentration (MCC) and collagen volume fraction (CVF) were measured at the sixteenth week, the twentieth week and the twenty eighth week after operation. The pathologic characterization of myocardial Ⅰ type and Ⅲ type collagen was observed at the same time. Results All measured datas in 2K1C hypertension group were significantly higher than in shamo operated group (P<0.05 or 0.005). Compared with hypertension group, plasma AngⅡ concentration was significantly higher (P<0.05), but SBP, LVWI, MCC mainly Ⅰ type collagen, CVF and plasma Ald concentration in the valsartan group decreased significantly (P<0.05). Treatment with spironolactone lightly decreased SBP, LVWI, MCC and CVF in early, but significantly lowered LVWI, MCC and CVF (P<0.05), especially Ⅲ type collagen. Conclusions It indicated that development of the LVH and myocardial fibrosis is heterochronia. This study suggested AngⅡ and aldsterone play a vital role in hypertensive myocardial remodeling. AT 1 receptor mainly mediats type I collagen deposition while aldosterone receptor mainly mediates type Ⅲ collagen deposition.