Published Online
on May 5, 2003

A more recent version of this article appeared on May 20, 2003

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Submitted on January 16, 2003
Revised on March 27, 2003
Accepted on March 31, 2003

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

Yuichiro Adachi MS, Yoshihiko Saito MD^*, Ichiro Kishimoto MD, Masaki Harada MD, Koichiro Kuwahara MD, Nobuki Takahashi MD, Rika Kawakami MD, Michio Nakanishi MD, Yasuaki Nakagawa MD, Keiji Tanimoto MD, Yoshitomo Saitoh MD, Shinji Yasuno MD, Satoru Usami MD, Masaru Iwai MD, Masatsugu Horiuchi MD, and Kazuwa Nakao MD

From the Department of Medicine and Clinical Science (Y.A., Y. Saito, I.K., M. Harada., K.K., N.T., R.K., M.N., Y.N., K.T., Y. Saitoh, S.Y., S.U., K.N.), Kyoto University Graduate School of Medicine, Kyoto, Japan; and the Department of Medical Biochemistry (M.I., M. Horiuchi), Ehime University School of Medicine, Ehime, Japan.

^* To whom correspondence should be addressed. E-mail: yssaito{at}nmu-gw.naramed-u.ac.jp.

Background--Angiotensin II plays a prominent role in the progression of heart failure after acute myocardial infarction (AMI). Although both angiotensin type 1 (AT₁) and type 2 (AT₂) receptors are known to be present in the heart, comparatively little is known about the latter. We therefore examined the role played by AT₂ receptors in post-AMI heart failure.

Methods and Results--In wild-type mice subjected to AMI by coronary artery ligation, AT₂ receptor immunoreactivity is upregulated in the infarct and border areas. Among AT₂ 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 AT₂^-/- significantly higher than in wild-type mice, as were their lung weights, and histological examination revealed marked pulmonary congestion in the AT₂^-/- mice. Cardiac function was significantly decreased in AT₂^-/- mice 2 days after AMI.

Conclusions--AT₂ receptor deficiency exacerbates short-term death rates and heart failure after experimental AMI in mice. The AT₂ receptor may thus exert a protective effect on the heart after AMI.

Key words: angiotensin • myocardial infarction • heart failure

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