Relationship between ACE/ACE2 in congestive heart failure rats and effect of carvedilol

Objectives To explore the relationship between ACE/ACE2 in congestive heart failure rats after myocardial infarction and the treatment effect of Carvedilol. Methods The rat heart failure model was induced by acute myocardial infarction(AMI)through ligating the left anterior descending coronary artery. One month after operation,rats were randomized to CHF placebo group and carvedilol group. Sham-operated rats were used as the control group. Then we evaluates the following indexes at 8th week:(1)Hemodynamics;(2)Body mass and left ventricular mass index;(3)The circulate and cardiac level of angiotensin Ⅱ;(4)ACE and ACE2 gene and protein expression using RT-PCR and Western Blot. Results The cirlutation and cardiac angiotentin Ⅱ level were increased significantly in CHF placebo group than sham-operation group(P 0.01=, The ACE and ACE2 mRNA and protein were increased in CHF placebo group than sham-operation group (P0.05,P0.01=, the ratio of ACE/ACE2 was elevated. The hemodynamics parameters of carvedilol group improved significantly than CHF placebo group (P 0.01=. The Ang Ⅱ level of carvedilol group was decreased obviously compared with CHF placebo group(P 0.05=. The level of ACE mRNA and protein were decreased significantly in carvedilol group(P 0.01=. The level of ACE2 mRNA and protein were increased most significantly in carvedilol group(P 0.01). The ratio of ACE/ACE2 was decreased. Conclusions The ACE and ACE2 gene and protein expression were up-regulated in CHF rats, the ratio of ACE/ACE2 was elevated. Carvedilol can down-regulate the expression of ACE and up-regulate the expression of ACE2, then the ratio of ACE/ACE2 decrease. This is the new explanation of the mechanism of the drug.