Effects Of Benazepril And Irbesartan On Myocardial Remodeling And Its Mechanisms In Chronic Heart Failure Rats

Objective To observe the effects of benazepril and Irbesartan on the myocardial remodeling and related mechanisms in Chronic Heart Failure Rats. And to investigate the expressions of AT1R,AT2R,ACE2,p-38MAPK and p-p38MAPK proteins in myocardium.Methods The cardiac failure animal model in rats were made by partially banding abdominal aorta to get pressure load. The animals were divided into five groups: the control group(Con), the model group (Mod),the Benazepril group(Ben 10mg·kg-1·d-1), the Irbesartan group(Irb 50mg·kg-1·d-1) and the combination group(Com Ben 5mg·kg-1·d-1 + Irb 25mg·kg-1·d-1), with drugs treated of 8 weeks. The arterial systolic pressure was measured using the tail-cuff method every two weeks. Cardiac geometry and function was evaluated with the echocardiographic system. Left ventricular catheter was placed via right common carotid artery and hemodynamics parameters were determined. Then, Rats were sacrificed and hearts were harvested. Heart weight index and area of cadiocytes were examined to compare the effects on myocardial hypertrophy. Meanwhile, the content of myocardial hydroxyproline was measured. The amount of cross-linked collagen in the myocardium was determined using the limited pepsin degradation properties. Besides, concentration of AngⅡin plasma and myocardium was measured by radioimmunity method. The expression of type I collagen,type III collagen,AT1R and AT2R protein in myocardium were investigated by immunohistochemistric assays. The expressions of AT1R,AT2R,ACE2,p-38MAPK and p-p38MAPK proteins were detected using western-blot analysis.Results 1. The arterial systolic pressures were decreased in the Mod and the treatment groups, but with no statistical significance.2. The LVSD,LVDD,LVEDP of the Mod were significantly increased, but the EF were decreased; Compared with the Mod, the LVSD,LVDD,LVEDP were significantly decreased while the EF were increased in the treatment groups, and the Com were superior than Ben or Irb groups.3. The cardiac index,the area of cardiocyte,the content of myocardial hydroxyproline,CVF,PVCA and the amount of cross-linked collagen were increased in the Mod but deceased in the treatment groups. And the Com had the synergic effects to ameliorate myocardial hypertrophy and myocardial fibrosis.4. Concertration of AngⅡin plasma and myocardium was down-regulated after the treatment of benazepril, and that was also dimineshed equally after the combined treatment, but augmented after the treatment of Irbesartan.5. Type I collagen,type III collagen,AT1R,AT2R,ACE2 and p-p38MAPK proteins were augmented while p-38MAPK proteins had no obviously change in the Mod. Compared with the Mod, Type I collagen,type III collagen,AT1R and p-p38MAPK proteins were obviously reduced while AT2R and ACE2 proteins were significantly augmented in the treatment groups. And the Com had the synergic effects.Conclusion There is a synergistic effect of attenuating cardiac ventricle remodeling and improving cardiac function in Chronic Heart Failure Rats by combined use of benazepril and Irbesartan. It may be related to the regulation of angiotensinⅡand the expressions of type I collagen,type III collagen,AT1R,AT2R,ACE2,p-38MAPK and p-p38MAPK proteins.