This Article Full Text Full Text (PDF) All Versions of this Article: 43/6/1162    most recent 01.HYP.0000128531.39964.c0v1 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 Booz, G. W. Search for Related Content PubMed PubMed Citation Articles by Booz, G. W. Pubmed/NCBI databases Compound via MeSH Substance via MeSH Related Collections Other myocardial biology ACE/Angiotension receptors Hypertrophy

(Hypertension. 2004;43:1162.)
© 2004 American Heart Association, Inc.

Editorial Commentaries

Cardiac Angiotensin AT₂ Receptor

What Exactly Does It Do?

From the Cardiovascular Research Institute of the Texas A&M, University System Health Science Center College of Medicine, Scott & White Hospital and Clinic, and the Central Texas Veterans Health Care System, Temple.

Correspondence to George W. Booz, PhD, Texas A&M University System Health Science Center, College of Medicine, Cardiovascular Research Institute, Division of Molecular Cardiology, 1901 South 1st Street, Bldg 205, Temple, TX 76504 E-mail gbooz@medicine.tamu.edu

An extract of the first 250 words of the full text is provided, because this article has no abstract.

Angiotensin II (Ang II) has multiple actions in the heart that affect cardiac remodeling and contractility, most of which can be attributed to activation of the Ang II type-1 (AT₁) receptor.¹ This 7-transmembrane-domain, G-protein-coupled receptor activates multiple intracellular signaling pathways that encompass calcium, phospholipids, kinases, and reactive oxygen species. But cardiac cells also express a second major Ang II membrane receptor, namely type-2 (AT₂), which despite being cloned more than a decade ago, remains something of an enigma as far as what function it plays in normal or diseased hearts.² AT₁ and AT₂ exhibit only 30% primary sequence homology, but both belong to the class A rhodopsin-like family of G-protein-coupled receptors and have similar high affinities for Ang II in the nanomolar range. However, the similarity ends there. The 2 receptors differ in which heterotrimeric G-proteins they preferentially activate, whether they undergo internalization on ligand binding, and the repertoire of signaling events each activates. In contrast to AT₁, only 4 major signaling mechanisms have been linked to AT₂: activation of protein phosphatases and protein dephosphorylation, regulation of the bradykinin-nitric-oxide-cGMP system, activation of phospholipase A₂ (PLA₂) and arachidonic acid release, and sphingolipid-derived ceramide formation.¹ Which mechanism predominates appears to be cell-type specific.

Because AT₂ couples to phosphatase activation whereas AT₁ activates various kinases, it is not surprising that in a variety of cell types the 2 receptors appear to be mutually antagonistic. In the early 1990s there were many reports demonstrating that Ang II has growth-promoting . . . [Full Text of this Article]

This article has been cited by other articles:

				M. S. Carneiro-Ramos, G. P. Diniz, J. Almeida, R. L. P. Vieira, S. V. B. Pinheiro, R. A. Santos, and M. L. M. Barreto-Chaves Cardiac angiotensin II type I and type II receptors are increased in rats submitted to experimental hypothyroidism J. Physiol., August 15, 2007; 583(1): 213 - 223. [Abstract] [Full Text] [PDF]

				S. A. Reini, C. E. Wood, E. Jensen, and M. Keller-Wood Increased maternal cortisol in late-gestation ewes decreases fetal cardiac expression of 11beta-HSD2 mRNA and the ratio of AT1 to AT2 receptor mRNA Am J Physiol Regulatory Integrative Comp Physiol, December 1, 2006; 291(6): R1708 - R1716. [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]

				T. L. Reudelhuber The Continuing Saga of the AT2 Receptor: A Case of the Good, the Bad, and the Innocuous Hypertension, December 1, 2005; 46(6): 1261 - 1262. [Full Text] [PDF]

				R. M. Carey Cardiovascular and Renal Regulation by the Angiotensin Type 2 Receptor: The AT2 Receptor Comes of Age Hypertension, May 1, 2005; 45(5): 840 - 844. [Full Text] [PDF]

				P. J. Harvey, B. L. Morris, J. A. Miller, and J. S. Floras Estradiol Induces Discordant Angiotensin and Blood Pressure Responses to Orthostasis in Healthy Postmenopausal Women Hypertension, March 1, 2005; 45(3): 399 - 405. [Abstract] [Full Text] [PDF]

				G. W. Booz Putting the Brakes on Cardiac Hypertrophy: Exploiting the NO-cGMP Counter-Regulatory System Hypertension, March 1, 2005; 45(3): 341 - 346. [Abstract] [Full Text] [PDF]