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(Hypertension. 1998;31:45.)
© 1998 American Heart Association, Inc.

Scientific Contributions

Increased Cardiac Angiotensin II Receptors in Angiotensinogen-Deficient Mice

Yoichi Sumida; Satoshi Umemura; Kouichi Tamura; Minoru Kihara; Shun-ichi Kobayashi; Tomoaki Ishigami; Machiko Yabana; Nobuo Nyui; Hisao Ochiai; Akiyoshi Fukamizu; Hitoshi Miyazaki; Kazuo Murakami; Masao Ishii

From the Second Department of Internal Medicine, Yokohama City University School of Medicine (Y.S., S.U., K.T., M.K., S.K., T.I., M.Y., N.N., H.O., M.I.), Yokohama, and the Institute of Applied Biochemistry (A.F., K.M.) and the Gene Experiment Center (H.M.), University of Tsukuba, Ibaraki, Japan.

Correspondence to Satoshi Umemura, MD, Second Department of Internal Medicine, Yokohama City University School of Medicine, 3–9, Fukuura, Kanazawa-ku, Yokohama 236, Japan.

Abstract—Two subtypes of angiotensin II (Ang II) receptors, type 1 (AT₁-R) and type 2 (AT₂-R), have been identified in the heart. However, little is known about the regulation of cardiac AT₁-R and AT₂-R by Ang II in vivo. Thus, we examined cardiac AT₁-R and AT₂-R in angiotensinogen-deficient (Atg-/-) mice that are hypotensive and lack circulating Ang II. Cardiac Ang II receptors (Ang II-R) were assessed by radioligand binding with ¹²⁵I-[Sar¹,Ile⁸]–Ang II in plasma membrane fractions. AT₁-R and AT₂-R were distinguished using their specific antagonists CV-11974 and PD123319, respectively. Total densities of Ang II-R and AT₁-R density were significantly greater in the Atg-/- mice than Atg+/+ mice (31.1±2.8 versus18.8±2.1, 28.7±3.0 versus16.9±2.3 fmol/mg protein, P<.01, respectively), and AT₂-R showed a slight but not significant increase in Atg-/- mice relative to Atg+/+ control animals. K_d values were not different between the two groups. In contrast to binding experiments, levels of Ang II type 1a receptor (AT_1a-R) and AT₂-R mRNA did not differ between Atg-/- and Atg+/+ mice. These results suggest that lack of Ang II may upregulate AT₁-R through translational and/or posttranslational mechanisms in Atg-/- mice.

Key Words: angiotensin II • receptors, angiotensin II • angiotensinogen • mice

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