Cardioprotective role of AT2 receptor in postinfarction left ventricular remodeling.
The aim of this study was to determine the role of the AT2 receptor (AT2R) in left ventricular (LV) remodeling after myocardial infarction (MI). The left anterior descending arteries were ligated in AT2R gene knockout (Agtr2-) and wild-type (Agtr2+) mice. The LV remodeling was evaluated by echocardiography and histology over a period of 2 weeks after MI. The infarct sizes in hearts excised from Agtr2+ and Agtr2- mice on day 1 were similar. The mortality rate of Agtr2- mice (62.9%) on day 14 after MI was significantly (P<0.05) higher than that of Agtr2+ mice (39.7%). Accordingly, LV/body weight ratios (3.7+/-0.2 versus 3.0+/-0.1 on day 14) and LV end-diastolic (4.8+/-0.3 versus 3.9+/-0.4 mm on day 7) and end-systolic (4.4+/-0.3 versus 3.2+/-0.6 mm on day 7) dimensions evaluated by echocardiography were significantly greater in Agtr2- than in Agtr2+ mice. The rates of ventricular arrhythmia, rates of cardiac rupture, and blood pressures in the 2 strains were similar after MI. Myocyte cross-sectional areas were increased after MI, but the magnitudes were similar in Agtr2+ and Agtr2- mice, indicating the greater increases in LV dimensions and weight in Agtr2- mice are due to elongation of myocyte length and/or an increase in the interstitial weight (including vasculatures, infiltrated cells, and interstitial fluid). Interstitial fibrosis in remote myocardium was not evident in either strain. These results indicate AT2R plays a significant role in the protection against early development of LV dilation, thereby reducing the early mortality rate after MI.
Oishi
Yoshihiko
Y
Department of Clinical Laboratory Medicine, Hiroshima University Graduate School of Biomedical Sciences, Hiroshima, Japan.
Ozono
Ryoji
R
Yano
Yoko
Y
Teranishi
Yasuhiro
Y
Akishita
Masahiro
M
Horiuchi
Masatsugu
M
Oshima
Tetsuya
T
Kambe
Masayuki
M
D000818:Animals; D006332:Cardiomegaly / Q000473:pathology; D002316:Cardiotonic Agents; D005355:Fibrosis; D006439:Hemodynamics; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009203:Myocardial Infarction / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology; D032383:Myocytes, Cardiac / Q000473:pathology; D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2; D011945:Receptors, Angiotensin / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D015996:Survival Rate; D020257:Ventricular Remodeling
D002316:Cardiotonic Agents; D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2; D011945:Receptors, Angiotensin