血管紧张素Ⅱ受体在压力超负荷致左室肥大中的作用

Role of angiotensin Ⅱ receptors in overload pressure-induced left ventricular hypertrophy

目的 :探讨血管紧张素Ⅱ受体 (ATRs)在压力超负荷致左室肥大中的作用。方法 :采用大鼠腹主动脉缩窄模型 ,通过放免法测心肌组织血管紧张素Ⅱ (AngⅡ )含量 ,放射性配基结合分析法检测心肌组织ATRs及其亚型的变化。结果 :手术组AngⅡ含量显著增高 ,与左室重量指数 (LVMI)呈正相关 (r=0 80 66,P <0 .0 1)。ATRs最大结合容量 (Bmax)显著高于对照组 (P <0 .0 1) ,但两组之间的平衡解离常数 (kd)、血管紧张素Ⅱ 1型受体 (AT1R)和血管紧张素Ⅱ 2型受体 (AT2 R)之间的比例无显著差异。非肽类AT1R拮抗剂Irbesartan可显著抑制AngⅡ的升高和左室肥大 ,非肽类AT2 R拮抗剂CGP4 2 112A则无此作用。结论 :压力超负荷时心肌组织ATRs上调 ,AngⅡ致左室肥大的作用主要由AT1R介导。

AIM and METHODS: To investigate the role of angiotensin Ⅱ recepters(ATRs) in overload pressure-induced left ventricular hypertrophy. The rat abdominal aortic constraction model was adopted. At 10th week after operating, angiotensin Ⅱ in myocardium was measured by radioimmunoassay,tissue ATRs and its subtype were analysed by radioligand binding assay. RESULTS: The AngⅡ content in the operated group was significantly higher than that of the control group, LVMI was positively correlated with AngⅡ(r=0.8066,P<0.01).The maximal binding capacity of ATRs in the operated group was significantly higher than that of the control group(P<0.01). However,the equilibrium dissociation constant(kd) and ratio of AT 1R to AT 2R in these two groups had no significantly different. Left ventricular hypertrophy was significantly reduced by AT 1R antagonist irbesartan,and not influenced by AT 2R antagonist CGP42112A. CONCLUSION: These results suggested that left ventricular ATRs upregulate during pressure overload.The left ventricular hypertrophy induced by AngⅡis mainly mediated by AT 1R.