Angiotensin II Type 2 Receptor Deficiency Exacerbates Heart Failure and Reduces Survival After Acute Myocardial Infarction in Mice

Abstract

Background— Angiotensin II plays a prominent role in the progression of heart failure after acute myocardial infarction (AMI). Although both angiotensin type 1 (AT 1 ) and type 2 (AT 2 ) receptors are known to be present in the heart, comparatively little is known about the latter. We therefore examined the role played by AT 2 receptors in post-AMI heart failure. Methods and Results— In wild-type mice subjected to AMI by coronary artery ligation, AT 2 receptor immunoreactivity is upregulated in the infarct and border areas. Among AT 2 receptor-null (−/−) mice, the 7-day survival rate after AMI was significantly lower than among wild-type mice (43% versus 67%; P <0.05). All sham-operated animals of both genotypes survived through the study. Ventricular mRNA levels for brain natriuretic peptide were elevated in both genotypes 24 hours after coronary occlusion, with levels in AT 2 −/− significantly higher than in wild-type mice, as were their lung weights, and histological examination revealed marked pulmonary congestion in the AT 2 −/− mice. Cardiac function was significantly decreased in AT 2 −/− mice 2 days after AMI. Conclusions— AT 2 receptor deficiency exacerbates short-term death rates and heart failure after experimental AMI in mice. The AT 2 receptor may thus exert a protective effect on the heart after AMI.