(Circulation. 2000;102:1684.)
© 2000 American Heart Association, Inc.
Basic Science Reports |
Inhibitory Effect of Angiotensin II Type 2 Receptor on Coronary Arterial Remodeling After Aortic Banding in Mice
From Cardiovascular Research, Department of Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, Mass (M.A., L.Z., V.J.D., M.H.); and Department of Geriatric Medicine, Kyorin University School of Medicine, Tokyo (M.A.), Department of Medical Biochemistry, Ehime University School of Medicine, Ehime (M.I., W.L., M.H.), and Department of Geriatric Medicine, Graduate School of Medicine, University of Tokyo, Tokyo (Y.O.), Japan.
Correspondence to Masatsugu Horiuchi, MD, PhD, Department of Medical Biochemistry, Ehime University School of Medicine, Shigenobu, Onsen-gun, Ehime 791-0295, Japan. E-mail horiuchi{at}m.ehime-u.ac.jp
Background—The renin-angiotensin system is thought to be critical for the development of cardiac hypertrophy, whereas the role of the angiotensin II type 2 (AT2) receptor in the process is not defined. Using the AT2 receptor–null (Agtr2-) mouse, we tested the hypothesis that the AT2 receptor could exert an antigrowth effect in cardiac hypertrophy.
Methods and Results—Cardiac hypertrophy was induced
by suprarenal abdominal aortic banding in 10- to 12-week-old
Agtr2- and wild-type (Agtr2+) mice for 6
or 12 weeks. Carotid arterial pressure was not different
between the strains, although aortic banding increased
arterial pressure by 
40 mm Hg. Aortic banding
increased the heart-weight/body-weight ratio and the cross-sectional
area of cardiomyocytes by 15%, resulting in comparable
cardiomyocyte hypertrophy in the 2 strains. In
contrast, coronary arterial thickening and
perivascular fibrosis, determined by the media/lumen-area ratio and the
collagen/vessel-area ratio, respectively, were 50% greater in
Agtr2- than in Agtr2+ mice after
banding, whereas these parameters were similar in
sham-operated mice. Radioligand binding studies using the
whole heart and immunohistochemistry showed that AT2
receptor expression was limited and localized in the coronary
artery and perivascular region.
Conclusions—These results suggest that the AT2 receptor mediates an inhibitory effect on coronary arterial remodeling, such as medial hypertrophy and perivascular fibrosis in response to pressure overload, and an activation of the renin-angiotensin system.
Key Words: angiotensin • receptors • muscle, smooth • myocytes • collagen
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