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


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.
Department of Medicine and Clinical Science, Kyoto University Graduate School of Medicine, Kyoto, Japan.
Yuichiro
Y
Adachi
Yoshihiko
Y
Saito
Ichiro
I
Kishimoto
Masaki
M
Harada
Koichiro
K
Kuwahara
Nobuki
N
Takahashi
Rika
R
Kawakami
Michio
M
Nakanishi
Yasuaki
Y
Nakagawa
Keiji
K
Tanimoto
Yoshitomo
Y
Saitoh
Shinji
S
Yasuno
Satoru
S
Usami
Masaru
M
Iwai
Masatsugu
M
Horiuchi
Kazuwa
K
Nakao
D000208:Acute Disease; D000818:Animals; D004195:Disease Models, Animal; D018450:Disease Progression; D004452:Echocardiography; D004562:Electrocardiography; D005260:Female; D006333:Heart Failure / Q000175:diagnosis / Q000209:etiology / Q000503:physiopathology*; D006720:Homozygote; D008026:Ligation; D051379:Mice; D018345:Mice, Knockout; D009203:Myocardial Infarction / Q000150:complications / Q000175:diagnosis / Q000503:physiopathology; D020097:Natriuretic Peptide, Brain / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2; D011945:Receptors, Angiotensin / Q000032:analysis / Q000172:deficiency* / Q000235:genetics / Q000378:metabolism; D012720:Severity of Illness Index; D015996:Survival Rate
D012333:RNA, Messenger; D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2; D011945:Receptors, Angiotensin; D020097:Natriuretic Peptide, Brain