Effects Of Aldosterone Receptor Antagonism On The Intracardiac RAS System After Acute Myocardial Infarction In Rats

Objective To investigate the effects of the aldosterone receptor antagonism spironolactone on the changes of RASS after acute myocardial infraction and to explore the role of ACE2 expression after AMI.Methods We established the LV infarct in rats by ligation of the left anterior descending coronary artery.108 healthy male SD rats (12-15 weeks and 210-260g) in this study were randomly divided into Sham group (water,2ml/d in drinking, 6),AMI group (water,2ml/d in drinking,6 ) and Spironolactone group (Spi,spionolactone 20mg/kg/d,6 ).At the 48th hour,7th day ,14th day and 21st day,the following indexes were observed : RT-PCR was used to observe the gene expression of ACEmRNA, ACE2mRNA and AT1mRNA.AngⅡlevels of plasma and noninfarcted area of the ventricle were observed by radio- immunoassay.All data were analyzed with SPSS version 11.5 statistical software.The comparison among groups was analyzed by One-Way ANOVA and S-N-K test.Results 1 Masson's trichrome stains the collagen in blue and myocardium in red in AMI rats heart,at infracted zone the ventricular wall became markedly thin, presentation as AMI. 2 ACE2mRNA in the noninfarcted zoneCompared with Sham group, ACE2 mRNA was increased significantly in the AMI group and Spi group at 7d,14d,21d (p<0.01),but there were no significant difference at 48h(p>0.05). In comparison with AMI group, ACE2 mRNA was significantly increased by 10.6%(p<0.05),43.8% and 93.1%(p<0.01)respectively at 7d,14d and 21d in Spi group,but there were no change at 48h(p>0.05).3 ACE mRNA in the noninfarcted zoneCompared with Sham group, ACE mRNA was increased significantly in the AMI group and Spi group at 7d,14d,21d(p<0.01 or p<0.05),but there were no significant difference at 48h(p>0.05).In comparison with AMI group, ACE mRNA was significantly decreased by 23.9%(p<0.01)and 40.7%(p<0.01)respectively at 14d and 21d in Spi group,but there were no change at 48h and 7d(p>0.05).4 AT1 mRNA in the noninfarcted zoneCompared with Sham group, AT1 mRNA was increased significantly in the AMI group and Spi group at 7d,14d,21d (p<0.01),but there were no significant difference at 48h(p>0.05). In comparison with AMI group, AT1 mRNA has no change at 48h and 7d(p>0.05) but was significantly decreased by 26.7%(p<0.01)and 32.4%(p<0.01)respectively at 14d and 21d in Spi group ,but it was still higher than Sham group.5 The plasma AngⅡlevels and cardiac AngⅡThe plasma AngⅡlevels did not change obviously at 21d (p>0.05)。Compared with Sham group cardiac AngⅡwas increased significantly in the AMI group at 21d. In comparison with AMI group, cardiac AngⅡwas significantly decreased(p<0.01)but still higher than Sham group.Conclusion Our study demonstrates that a progressive activation of the local intracardiac RAS occurs after myocardial infarction. It may be a self-protected mechanism that ACE2mRNA levels increased in the noninfarcted area of the ventricle in compensation. The increased AngII of cardiac tissues may be an important factor for myocardial hypertrophy, and play an important role in the process of post-infarction ventricular remodeling.The use of spirolactone in AMI caused a reduction of ACEmRNA,AT1mRNA and AngII of cardiac tissues in the noninfarction area of rat heart after AMI. Spirolactone could increased the cardiac ACE2 mRNA levels which may be one of the mechamisms that spirolactone prevented left ventricular remodeling after AMI.