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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2002;22:49.)
© 2002 American Heart Association, Inc.

Vascular Biology

Effect of Angiotensin II Type 1 Receptor Blockade on Cardiac Remodeling in Angiotensin II Type 2 Receptor Null Mice

Lan Wu; Masaru Iwai; Hironori Nakagami; Rui Chen; Jun Suzuki; Masahiro Akishita; Marc de Gasparo; Masatsugu Horiuchi

From the Department of Medical Biochemistry (L.W., M.I., H.N., R.C., J.S., M.H.), Ehime University School of Medicine, Ehime, Japan; the Department of Geriatric Medicine (M.A.), Kyorin University School of Medicine, Tokyo, Japan; and MG Consulting Co (M.d.G.), Rossemaison, Switzerland.

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

To clarify the possible involvement of uninhibited angiotensin II (Ang II) type 2 (AT₂) receptor stimulation in the effects of an Ang II type 1 (AT₁) receptor blocker, valsartan, we examined the cardiovascular remodeling induced by aortic banding with the use of wild-type (Agtr2+) and AT₂ receptor null (Agtr2-) mice. Aortic banding caused cardiac hypertrophy in Agtr2+ and Agtr2- mice to a similar degree 6 weeks after surgery, whereas coronary arterial thickening and perivascular fibrosis were more exaggerated in Agtr2- mice. The AT₂ receptor was observed predominantly in the coronary arteries and perivascular region of Agtr2+ mice. Valsartan at a dose of 1 mg/kg per day, which did not influence systolic blood pressure, suppressed cardiac hypertrophy similarly in both strains. Valsartan inhibited coronary arterial thickening and perivascular fibrosis in both groups; however, the inhibitory effects of valsartan were significantly weaker in Agtr2- mice. The inhibitory effects of a nonselective Ang II receptor antagonist, [Sar¹,Ile⁸]-Ang II, on cardiac hypertrophy, coronary artery thickening, and perivascular fibrosis were not significantly different in Agtr2+ and Agtr2- mice. These results suggest that the improvement by valsartan of coronary arterial thickening and perivascular fibrosis after pressure overload is caused by uninhibited AT₂ receptor stimulation in addition to AT₁ receptor blockade.

Key Words: angiotensin • receptors • cardiomyocytes • fibrosis • coronary arteries

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