Inhibitory Effect of Angiotensin II Type 2 Receptor on Coronary Arterial Remodeling After Aortic Banding in Mice

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Abstract
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 ≈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.