血管紧张素AT_1受体阻断剂Valsartan对大鼠心肌梗死后心脏重构和左心室功能的保护作用(英文)

Effects of angiotensin AT_1 receptor antagonist,valsartan,on cardiac remodeling and left ventricular dysfunction after myocardial infarction in rats

目的 :评估新的血管紧张素AT1 受体阻断剂valsartan对大鼠心肌梗死后心脏的保护作用。方法 :将左冠状动脉结扎的雄性Wistar大鼠随机分为valsartan处理组 (n =1 2 )和生理盐水处理组 (n =1 2 ) ,处理开始于心肌梗死手术后 2 4h,并持续至心肌梗死后 6w。以假手术大鼠作为对照。将平均动脉血压、左心室舒张末期压力、左心室dP/dtmax、左心室内直径和周长、室间隔厚度、梗死面积、心肌间质胶原含量和相对心脏重量等参数作为评估指标。结果 :与假手术组大鼠比较 ,心肌梗死生理盐水处理组大鼠心脏肥大 ,左心室腔明显扩大 ,心肌间质胶原沉积和左心室功能严重损害。与心肌梗死生理盐水处理组比较 ,valsartan处理组大鼠心脏重量对体重率减小 ,心肌间质胶原含量减少 ,左心室舒张末期压力降低和心肌收缩力改善。但不能限制梗死面积和左心室扩张。结论 :Valsartan慢性处理可减弱心肌梗死大鼠的心脏重构和改善心脏功能 。

Objective:To assess the cardioprotective effects of a novel angiotensin AT 1 receptor antagonist,valsartan,in rats with myocardial infarction.Methods:Male Wistar rats that underwent coronary ligation were randomized to receive valsartan treatment(30 mg/kg) or placebo(physiological saline,1 ml/kg) 1 day after myocardial infarction. Treatment was continued up to 6 weeks after myocardial infarction. Sham operation rats served as controls. Mean arterial blood pressure(MAP),maximum rate of rise of the left ventricular pressure(dP/dt max ),left ventricular end diastolic pressure(LVEDP),inner diameter and circumference of left ventricle,septal thickness,infarct size,interstitial collagen and heart weight,heart weight to body weight ratio were measured at the end of the treatment.Results:Myocardial infarction induced cardiac hypertrophy,interstitial collagen deposition and left ventricular dilatation,and impaired left ventricular function. Valsartan treatment decreased heart weight and heart weight to body weight ratio,diminished interstitial collagen content,lowered LVEDP,and improved myocardial contractility(all P<0.05～0.01) compared to that of placebo treated infarct rats.Conclusion:The present results demonstrate that chronic treatment with the angiotensin AT 1 receptor antagonist valsartan can attenuate cardiac structural remodeling and improve left ventricular dysfunction after myocardial infarction in rats.