The Effect of Carvedilol on ACE2 Expression in Chronic Heart Failure Rats

Objective To explore the effect of carvedilol on ACE2 gene and protein expression in chronic heart failure rats after myocardial infarction.Methods The heart failure model was induced by acute myocardial infarc- tion (AMI) through ligating the left anterior descending coronary artery.One month after operation,rats were randomized to receive placebo or carvedilol 2 mg/(kg·d),by gavage.Sham-operated rats were used as the control group.Hemodynamies,body mass and left ventrieular mass index,plasma and myocardial level of angiotensin Ⅱ were determined.ACE2 gene and protein expression was assessed by using RT-PCR and Western Blot.Results The mortality of placebo and Carvedilol groups were 20%,compared with 0% in sham operated rats.Carvedilol significantly improved LVEDP,LVSP,+dp/dt_(max) and-dp/dt_(min) in CHF rats but all the hemodynamics data were still inferior than that of controls.Plasma and myocardial angiotensin Ⅱ level were increased significantly in CHF placebo rats than those of control rats (plasma Ang Ⅱ:CHF:194±19 vs controls:132±15 ng/L,myocardium Ang Ⅱ:CHF:6.7±0.4 vs control:3.8±0.3 ng/g,P0.01).ACE2 mRNA and protein were concomitantly in- creased (ACE2 mRNA:CHF:1.09±0.07 vs controls:0.81±0.06;ACE2 protein:CHF:0.68±0.08 vs controls: 0.54±0.07,P0.01),Carvedilol significantly improved hemonamic data(P0.01) and decreased myocardial Ang Ⅱ obviously (Carvedilol:6.0±0.5 vs CHF:6.7±0.4,P0.05),while the level of ACE2 mRNA and protein were increased significantly (Carvedilol:ACE2 mRNA:1.38±0.08 vs CHF:1.09±0.07,ACE2 protein:Carve- dilol:0.93±0.09 vs CHF:0.68±0.08,P all0.01).Conclusion ACE2 gene and protein expression were up- regulated in CHF rats.Carvedilol accentuate the upregulation of the expression of ACE2.Whether ACE2 upreg- ulation is a compensatory response,a beneficial factor for CHF,or just an associated phenomenon need futher investigation.