The Angiotensin II Type 2 Receptor Causes Constitutive Growth of Cardiomyocytes and Does Not Antagonize Angiotensin II Type 1 Receptor–Mediated Hypertrophy

D’Amore, Angelo, Black, M. Jane and Thomas, Walter G. (2005) The Angiotensin II Type 2 Receptor Causes Constitutive Growth of Cardiomyocytes and Does Not Antagonize Angiotensin II Type 1 Receptor–Mediated Hypertrophy. Hypertension, 46 6: 1347-1354. doi:10.1161/01.HYP.0000193504.51489.cf


Author D’Amore, Angelo
Black, M. Jane
Thomas, Walter G.
Title The Angiotensin II Type 2 Receptor Causes Constitutive Growth of Cardiomyocytes and Does Not Antagonize Angiotensin II Type 1 Receptor–Mediated Hypertrophy
Journal name Hypertension   Check publisher's open access policy
ISSN 0194-911X
Publication date 2005-11-14
Sub-type Article (original research)
DOI 10.1161/01.HYP.0000193504.51489.cf
Volume 46
Issue 6
Start page 1347
End page 1354
Total pages 8
Place of publication Baltimore, MD
Publisher Lippincott Williams & Wilkins for the American Heart Association
Language eng
Subject 060108 Protein Trafficking
060110 Receptors and Membrane Biology
060111 Signal Transduction
060199 Biochemistry and Cell Biology not elsewhere classified
060602 Animal Physiology - Cell
110201 Cardiology (incl. Cardiovascular Diseases)
110903 Central Nervous System
Abstract Angiotensin II (Ang II) has important actions on the heart via type 1 (AT1) and type 2 (AT2) receptors. The link between AT1 receptor activation and the hypertrophy of cardiomyocytes is accepted, whereas the contribution of the AT2 receptor, which reportedly antagonizes the AT1 receptor, is contentious. This ambiguity is primarily based on in vivo approaches, in which the direct effect of the AT2 receptor and its modulation of the AT1 receptor (at the level of the cardiomyocyte) are difficult to establish. In this study, we used adenoviruses encoding AT1 and AT2 to coexpress these receptors in isolated cardiomyocytes, allowing a direct examination of the consequence of varying AT1/AT2 stoichiometry on cardiomyocyte hypertrophy. In myocytes expressing only the AT1 receptor, Ang II stimulation promoted robust hypertrophy (increased protein:DNA ratio and phenotypic changes) via activation of mitogen-activated protein kinases (MAPKs). Titration of the AT2 receptor against the AT1 receptor did not inhibit Ang II–mediated cardiomyocyte hypertrophy. Instead, basal and Ang II–mediated hypertrophy was increased in line with the amplified expression of the AT2 receptor, indicating a capacity for the AT2 receptor to enhance basal cardiomyocyte growth. Indeed, expression of the AT2 receptor alone resulted in hypertrophy; remarkably, this was unaffected by Ang II stimulation or the AT2 receptor–specific ligands PD123319 and CGP42112. Although previous studies have indicated that the AT2 receptor can antagonize MAPK activation via the AT1 receptor, we found no evidence for this in cardiomyocytes. Thus, the AT2 receptor promotes ligand-independent, constitutive cardiomyocyte hypertrophy and does not directly antagonize the AT1 receptor in this setting.
Keyword angiotensin II
hypertrophy
myocytes
rats
receptors
Q-Index Code C1

Document type: Journal Article
Sub-type: Article (original research)
Collections: Excellence in Research Australia (ERA) - Collection
School of Biomedical Sciences Publications
 
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