This Article Full Text Full Text (PDF) All Versions of this Article: 107/19/2406    most recent 01.CIR.0000072763.98069.B4v1 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 Adachi, Y. Articles by Nakao, K. Search for Related Content PubMed PubMed Citation Articles by Adachi, Y. Articles by Nakao, K. Pubmed/NCBI databases Compound via MeSH Substance via MeSH Medline Plus Health Information Heart Failure Related Collections ACE/Angiotension receptors Heart failure - basic studies

(Circulation. 2003;107:2406.)
© 2003 American Heart Association, Inc.

Brief Rapid Communications

Angiotensin II Type 2 Receptor Deficiency Exacerbates Heart Failure and Reduces Survival After Acute Myocardial Infarction in Mice

Yuichiro Adachi, MS; Yoshihiko Saito, MD; Ichiro Kishimoto, MD; Masaki Harada, MD; Koichiro Kuwahara, MD; Nobuki Takahashi, MD; Rika Kawakami, MD; Michio Nakanishi, MD; Yasuaki Nakagawa, MD; Keiji Tanimoto, MD; Yoshitomo Saitoh, MD; Shinji Yasuno, MD; Satoru Usami, MD; Masaru Iwai, MD; Masatsugu Horiuchi, MD; Kazuwa Nakao, MD

From the Department of Medicine and Clinical Science (Y.A., Y. Saito, I.K., M. Harada., K.K., N.T., R.K., M.N., Y.N., K.T., Y. Saitoh, S.Y., S.U., K.N.), Kyoto University Graduate School of Medicine, Kyoto, Japan; and the Department of Medical Biochemistry (M.I., M. Horiuchi), Ehime University School of Medicine, Ehime, Japan.

Correspondence to Yoshihiko Saito, MD, First Department of Internal Medicine, Nara Medical University, 840 Shijo-cho Kashihara, Nara, 634-8582, Japan. E-mail yssaito{at}nmu-gw.naramed-u.ac.jp

Background— Angiotensin II plays a prominent role in the progression of heart failure after acute myocardial infarction (AMI). Although both angiotensin type 1 (AT₁) and type 2 (AT₂) receptors are known to be present in the heart, comparatively little is known about the latter. We therefore examined the role played by AT₂ receptors in post-AMI heart failure.

Methods and Results— In wild-type mice subjected to AMI by coronary artery ligation, AT₂ receptor immunoreactivity is upregulated in the infarct and border areas. Among AT₂ receptor-null (-/-) mice, the 7-day survival rate after AMI was significantly lower than among wild-type mice (43% versus 67%; P<0.05). All sham-operated animals of both genotypes survived through the study. Ventricular mRNA levels for brain natriuretic peptide were elevated in both genotypes 24 hours after coronary occlusion, with levels in AT₂^-/- significantly higher than in wild-type mice, as were their lung weights, and histological examination revealed marked pulmonary congestion in the AT₂^-/- mice. Cardiac function was significantly decreased in AT₂^-/- mice 2 days after AMI.

Conclusions— AT₂ receptor deficiency exacerbates short-term death rates and heart failure after experimental AMI in mice. The AT₂ receptor may thus exert a protective effect on the heart after AMI.

Key Words: angiotensin • myocardial infarction • heart failure

This article has been cited by other articles:

				E. Kaschina, A. Grzesiak, J. Li, A. Foryst-Ludwig, M. Timm, F. Rompe, M. Sommerfeld, U. R. Kemnitz, C. Curato, P. Namsolleck, et al. Angiotensin II Type 2 Receptor Stimulation: A Novel Option of Therapeutic Interference With the Renin-Angiotensin System in Myocardial Infarction? Circulation, December 9, 2008; 118(24): 2523 - 2532. [Abstract] [Full Text] [PDF]

				X. Yan, A. J. T. Schuldt, R. L. Price, I. Amende, F.-F. Liu, K. Okoshi, K. K. L. Ho, A. J. Pope, T. K. Borg, B. H. Lorell, et al. Pressure overload-induced hypertrophy in transgenic mice selectively overexpressing AT2 receptors in ventricular myocytes Am J Physiol Heart Circ Physiol, March 1, 2008; 294(3): H1274 - H1281. [Abstract] [Full Text] [PDF]

				L. Gomez, H. Thibault, A. Gharib, J.-M. Dumont, G. Vuagniaux, P. Scalfaro, G. Derumeaux, and M. Ovize Inhibition of mitochondrial permeability transition improves functional recovery and reduces mortality following acute myocardial infarction in mice Am J Physiol Heart Circ Physiol, September 1, 2007; 293(3): H1654 - H1661. [Abstract] [Full Text] [PDF]

				M. Takaoka, S. Uemura, H. Kawata, K.-i. Imagawa, Y. Takeda, K. Nakatani, N. Naya, M. Horii, S. Yamano, Y. Miyamoto, et al. Inflammatory Response to Acute Myocardial Infarction Augments Neointimal Hyperplasia After Vascular Injury in a Remote Artery Arterioscler. Thromb. Vasc. Biol., September 1, 2006; 26(9): 2083 - 2089. [Abstract] [Full Text] [PDF]

				S. Voros, Z. Yang, C. M. Bove, W. D. Gilson, F. H. Epstein, B. A. French, S. S. Berr, S. P. Bishop, M. R. Conaway, H. Matsubara, et al. Interaction between AT1 and AT2 receptors during postinfarction left ventricular remodeling Am J Physiol Heart Circ Physiol, March 1, 2006; 290(3): H1004 - H1010. [Abstract] [Full Text] [PDF]

				M. Iwai, R. Chen, Z. Li, T. Shiuchi, J. Suzuki, A. Ide, M. Tsuda, M. Okumura, L.-J. Min, M. Mogi, et al. Deletion of Angiotensin II Type 2 Receptor Exaggerated Atherosclerosis in Apolipoprotein E-Null Mice Circulation, September 13, 2005; 112(11): 1636 - 1643. [Abstract] [Full Text] [PDF]

				M. Gonzalez, L. Lobos, F. Castillo, L. Galleguillos, N. C. Lopez, and L. Michea High-Salt Diet Inhibits Expression of Angiotensin Type 2 Receptor in Resistance Arteries Hypertension, May 1, 2005; 45(5): 853 - 859. [Abstract] [Full Text] [PDF]

				M. Nakayama, X. Yan, R. L. Price, T. K. Borg, K. Ito, A. Sanbe, J. Robbins, and B. H. Lorell Chronic ventricular myocyte-specific overexpression of angiotensin II type 2 receptor results in intrinsic myocyte contractile dysfunction Am J Physiol Heart Circ Physiol, January 1, 2005; 288(1): H317 - H327. [Abstract] [Full Text] [PDF]

				O. Johren, A. Dendorfer, and P. Dominiak Cardiovascular and renal function of angiotensin II type-2 receptors Cardiovasc Res, June 1, 2004; 62(3): 460 - 467. [Abstract] [Full Text] [PDF]

				C. M. Bove, Z. Yang, W. D. Gilson, F. H. Epstein, B. A. French, S. S. Berr, S. P. Bishop, H. Matsubara, R. M. Carey, and C. M. Kramer Nitric Oxide Mediates Benefits of Angiotensin II Type 2 Receptor Overexpression During Post-Infarct Remodeling Hypertension, March 1, 2004; 43(3): 680 - 685. [Abstract] [Full Text] [PDF]

				M. Brede, W. Roell, O. Ritter, F. Wiesmann, R. Jahns, A. Haase, B. K. Fleischmann, and L. Hein Cardiac Hypertrophy Is Associated With Decreased eNOS Expression in Angiotensin AT2 Receptor-Deficient Mice Hypertension, December 1, 2003; 42(6): 1177 - 1182. [Abstract] [Full Text] [PDF]

				X. Yan, R. L. Price, M. Nakayama, K. Ito, A. J. T. Schuldt, W. J. Manning, A. Sanbe, T. K. Borg, J. Robbins, and B. H. Lorell Ventricular-specific expression of angiotensin II type 2 receptors causes dilated cardiomyopathy and heart failure in transgenic mice Am J Physiol Heart Circ Physiol, November 1, 2003; 285(5): H2179 - H2187. [Abstract] [Full Text] [PDF]