Inhibitory effect of angiotensin II type 2 receptor on coronary arterial remodeling after aortic banding in mice.
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 (AT(2)) receptor in the process is not defined. Using the AT(2) receptor-null (Agtr2-) mouse, we tested the hypothesis that the AT(2) 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 approximately 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 AT(2) receptor expression was limited and localized in the coronary artery and perivascular region. CONCLUSIONS: These results suggest that the AT(2) 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.
Akishita, M; Iwai, M; Wu, L; Zhang, L; Ouchi, Y; Dzau, VJ; Horiuchi, M
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