Angiotensin II type 2 receptor deficiency exacerbates heart failure and reduces survival after acute myocardial infarction in mice

• Published in: Circulation (New York, N.Y.) Vol. 107; no. 19; pp. 2406 - 2408
• Main Authors: ADACHI, Yuichiro, SAITO, Yoshihiko, SAITOH, Yoshitomo, YASUNO, Shinji, USAMI, Satoru, IWAI, Masaru, HORIUCHI, Masatsugu, NAKAO, Kazuwa, KISHIMOTO, Ichiro, HARADA, Masaki, KUWAHARA, Koichiro, TAKAHASHI, Nobuki, KAWAKAMI, Rika, NAKANISHI, Michio, NAKAGAWA, Yasuaki, TANIMOTO, Keiji
• Format: Journal Article
• Language: English
• Published: Hagerstown, MD Lippincott Williams & Wilkins 20.05.2003; American Heart Association, Inc
• Subjects: Acute Disease; Animals; Biological and medical sciences; Cardiology. Vascular system; Coronary heart disease; Disease Models, Animal; Disease Progression; Echocardiography; Electrocardiography; Female; Heart; Heart Failure - diagnosis; Heart Failure - etiology; Heart Failure - physiopathology; Homozygote; Ligation; Medical sciences; Mice; Mice, Knockout; Myocardial Infarction - complications; Myocardial Infarction - diagnosis; Myocardial Infarction - physiopathology; Natriuretic Peptide, Brain - genetics; Natriuretic Peptide, Brain - metabolism; Receptor, Angiotensin, Type 1; Receptor, Angiotensin, Type 2; Receptors, Angiotensin - analysis; Receptors, Angiotensin - deficiency; Receptors, Angiotensin - genetics; Receptors, Angiotensin - metabolism; RNA, Messenger - metabolism; Severity of Illness Index; Survival Rate; Heart failure; Prognosis; Infarct; Acute; Rodentia; myocardial infarction; Cardiovascular disease; Coronary heart disease; Myocardial disease; Survival; AT2 angiotensin receptor; Vertebrata; Mammalia; Mouse; Follow up study; Heart disease; Animal; Myocardium; angiotensin
• ISSN: 0009-7322; 1524-4539
• DOI: 10.1161/01.CIR.0000072763.98069.B4

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. 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. 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.