This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Jin, X.-Q. Articles by Miyazaki, H. Search for Related Content PubMed PubMed Citation Articles by Jin, X.-Q. Articles by Miyazaki, H. Pubmed/NCBI databases Gene GEO Profiles HomoloGene UniGene Compound via MeSH Substance via MeSH Hazardous Substances DB (L)-ARGININE Related Collections ACE/Angiotension receptors

(Hypertension. 2002;39:1021.)
© 2002 American Heart Association, Inc.

Scientific Contributions

Angiotensin II Type 2 Receptor Gene Transfer Downregulates Angiotensin II Type 1a Receptor in Vascular Smooth Muscle Cells

Xue-Qing Jin; Noboru Fukuda; Jin-Zi Su; Yi-Mu Lai; Ryo Suzuki; Yoshiko Tahira; Hiroto Takagi; Yukihiro Ikeda; Katsuo Kanmatsuse; Hitoshi Miyazaki

From the Second Department of Internal Medicine, Nihon University School of Medicine (X-Q.J., N.F., J-Z.S., Y-M.L., R.S., Y.T., H.T., Y.I., K.K.), Tokyo, Japan; and Gene Experiment Center, University of Tsukuba (H.M.), Ibaraki, Japan.

Correspondence to Noboru Fukuda, MD, PhD, Second Department of Internal Medicine, Nihon University School of Medicine, Ooyaguchi-kamimachi 30-1, Itabashi-ku, Tokyo 173-8610, Japan. E-mail nhukuda{at}med.nihon-u.ac.jp

Two distinct subtypes of angiotensin (Ang) II receptors, type 1 (AT₁) and type 2 (AT₂), have been identified. Vascular smooth muscle cells (VSMCs) usually express AT₁ receptor. To elucidate the direct effects of the AT₂ receptor on the AT₁ receptor in VSMCs, we transfected AT₂ receptor gene into cultured rat VSMCs. Overexpression of AT₂ receptor significantly decreased expression of AT_1a receptor at both the mRNA and protein levels in the presence and absence of Ang II in VSMCs. Overexpression of AT₂ receptor increased expression of bradykinin and inducible NO in the presence and absence of Ang II in VSMCs. Bradykinin B₂ receptor antagonist HOE–140 and NO synthase inhibitor N-nitro-L-arginine methyl ester (L-NAME) inhibited the decreases in AT_1a receptor expression by the overexpression of AT₂ receptor in VSMCs. L-Arginine augmented the decrease in AT_1a receptor expression. Overexpression of AT₂ receptor suppressed basal DNA synthesis and proliferation of VSMCs and abolished response of DNA synthesis to Ang II in VSMCs. Our results demonstrate that overexpression of the AT₂ receptor downregulates AT_1a receptor expression in rat VSMCs in a ligand-independent manner that is mediated by the bradykinin/NO pathway. Downregulation of AT_1a receptor is a novel mechanism by which the AT₂ receptor regulates growth and metabolism of VSMCs.

Key Words: receptors, angiotensin II • angiotensin II • muscle, smooth, vascular • nitric oxide • bradykinin

This article has been cited by other articles:

				T. Backlund, P. Lakkisto, E. Palojoki, T. Gronholm, A. Saraste, P. Finckenberg, E. Mervaala, I. Tikkanen, and M. Laine Activation of protective and damaging components of the cardiac renin-angiotensin system after myocardial infarction in experimental diabetes Journal of Renin-Angiotensin-Aldosterone System, June 1, 2007; 8(2): 66 - 73. [Abstract] [PDF]

				C. Savoia, R. M. Touyz, M. Volpe, and E. L. Schiffrin Angiotensin Type 2 Receptor in Resistance Arteries of Type 2 Diabetic Hypertensive Patients Hypertension, February 1, 2007; 49(2): 341 - 346. [Abstract] [Full Text] [PDF]

				C. Warnecke, P. Mugrauer, D. Surder, J. Erdmann, C. Schubert, and V. Regitz-Zagrosek Intronic ANG II type 2 receptor gene polymorphism 1675 G/A modulates receptor protein expression but not mRNA splicing Am J Physiol Regulatory Integrative Comp Physiol, December 1, 2005; 289(6): R1729 - R1735. [Abstract] [Full Text] [PDF]

				A. D'Amore, M. J. Black, and W. G. Thomas The Angiotensin II Type 2 Receptor Causes Constitutive Growth of Cardiomyocytes and Does Not Antagonize Angiotensin II Type 1 Receptor-Mediated Hypertrophy Hypertension, December 1, 2005; 46(6): 1347 - 1354. [Abstract] [Full Text] [PDF]

				N. S Anavekar and S. D Solomon Angiotensin II receptor blockade and ventricular remodelling Journal of Renin-Angiotensin-Aldosterone System, March 1, 2005; 6(1): 43 - 48. [Abstract] [PDF]

				D. Perlegas, H. Xie, S. Sinha, A. V. Somlyo, and G. K. Owens ANG II type 2 receptor regulates smooth muscle growth and force generation in late fetal mouse development Am J Physiol Heart Circ Physiol, January 1, 2005; 288(1): H96 - H102. [Abstract] [Full Text] [PDF]

				Y. Tan, F. N. Hutchison, and A. A. Jaffa Mechanisms of angiotensin II-induced expression of B2 kinin receptors Am J Physiol Heart Circ Physiol, March 1, 2004; 286(3): H926 - H932. [Abstract] [Full Text] [PDF]

				Y. Oishi, R. Ozono, Y. Yano, Y. Teranishi, M. Akishita, M. Horiuchi, T. Oshima, and M. Kambe Cardioprotective Role of AT2 Receptor in Postinfarction Left Ventricular Remodeling Hypertension, March 1, 2003; 41(3): 814 - 818. [Abstract] [Full Text] [PDF]

				S. Kurisu, R. Ozono, T. Oshima, M. Kambe, T. Ishida, H. Sugino, H. Matsuura, K. Chayama, Y. Teranishi, O. Iba, et al. Cardiac Angiotensin II Type 2 Receptor Activates the Kinin/NO System and Inhibits Fibrosis Hypertension, January 1, 2003; 41(1): 99 - 107. [Abstract] [Full Text] [PDF]

				J.-Z. Su, N. Fukuda, X.-Q. Jin, Y.-M. Lai, R. Suzuki, Y. Tahira, H. Takagi, Y. Ikeda, K. Kanmatsuse, and H. Miyazaki Effect of AT2 Receptor on Expression of AT1 and TGF-{beta} Receptors in VSMCs from SHR Hypertension, December 1, 2002; 40(6): 853 - 858. [Abstract] [Full Text] [PDF]