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 Lévy, B. I. Search for Related Content PubMed PubMed Citation Articles by Lévy, B. I. Related Collections Cardiovascular Pharmacology ACE/Angiotension receptors Clinical Studies

(Circulation. 2004;109:8-13.)
© 2004 American Heart Association, Inc.

Review: Current Perspective

Can Angiotensin II Type 2 Receptors Have Deleterious Effects in Cardiovascular Disease?

Implications for Therapeutic Blockade of the Renin–Angiotensin System

Bernard I. Lévy, MD, PhD

From Institut National de la Santé et de la Recherche Médicale (INSERM) U 541, Hôpital Lariboisière, IFR Circulation-Lariboisière, Université Paris 7-Denis Diderot, Paris, France.

Correspondence to Professor Bernard I. Lévy, INSERM U541, 41 Bd de la Chapelle, 75475 Paris, Cedex 10, France. E-mail levy@infobiogen.fr

Key Words: receptors • angiotensin • cardiovascular diseases • hypertrophy

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

	Introduction

 
The renin–angiotensin system (RAS) plays a major role in regulating the cardiovascular system, and disorders of the RAS contribute largely to the pathophysiology of hypertension, renal diseases, and chronic heart failure. Two subtypes of angiotensin II (Ang II) receptors have been defined on the basis of their differential pharmacological and biochemical properties: Ang II type 1 receptors (AT₁), which are involved in most of the well-known physiological effects of Ang II, and Ang II type 2 receptors (AT₂), which have a less well-defined role but appear capable of counterbalancing some of the effects of AT₁ stimulation.

The 2 receptors, both of which belong to the superfamily of G-protein–coupled receptors, are believed to have different signaling pathways and different functions.¹ AT₁ transactivates growth pathways and mediates major Ang II effects such as vasoconstriction, increased cardiac contractility, renal tubular sodium reabsorption, cell proliferation, vascular and cardiac hypertrophy, inflammatory responses, and oxidative stress. AT₂ is believed to induce essentially opposite effects, including vasodilation and antigrowth and antihypertrophic effects,^1–3 and to play a significant role in blood pressure (BP) regulation.⁴

The 2 major pharmacological inhibitors of the RAS, which are now important elements in the treatment of hypertension and cardiovascular disease, are ACE inhibitors and angiotensin receptor blockers (ARBs). These 2 classes of drugs have different effects on the RAS: suppression of Ang II production by ACE inhibitors reduces activation of both Ang II receptor subtypes, whereas ARBs preferentially block AT₁ and leave AT₂ unopposed. Long-term administration of ARBs results in a . . . [Full Text of this Article]

This article has been cited by other articles:

				L. Zhang, H. Tu, and Y.-L. Li Angiotensin II enhances hyperpolarization-activated currents in rat aortic baroreceptor neurons: involvement of superoxide Am J Physiol Cell Physiol, January 1, 2010; 298(1): C98 - C106. [Abstract] [Full Text] [PDF]

				T. Kimura, C. Mogi, H. Tomura, A. Kuwabara, D.-S. Im, K. Sato, H. Kurose, M. Murakami, and F. Okajima Induction of Scavenger Receptor Class B Type I Is Critical for Simvastatin Enhancement of High-Density Lipoprotein-Induced Anti-Inflammatory Actions in Endothelial Cells J. Immunol., November 15, 2008; 181(10): 7332 - 7340. [Abstract] [Full Text] [PDF]

				J. S. Troutt, W. E. Alborn, M. K. Mosior, J. Dai, A. T. Murphy, T. P. Beyer, Y. Zhang, G. Cao, and R. J. Konrad An apolipoprotein A-I mimetic dose-dependently increases the formation of pre{beta}1 HDL in human plasma J. Lipid Res., March 1, 2008; 49(3): 581 - 587. [Abstract] [Full Text] [PDF]

				B. Burstein and S. Nattel Atrial Fibrosis: Mechanisms and Clinical Relevance in Atrial Fibrillation J. Am. Coll. Cardiol., February 26, 2008; 51(8): 802 - 809. [Abstract] [Full Text] [PDF]

				Q. Zhang, F. He, R. Kuruba, X. Gao, A. Wilson, J. Li, T. R. Billiar, B. R. Pitt, W. Xie, and S. Li FXR-mediated regulation of angiotensin type 2 receptor expression in vascular smooth muscle cells Cardiovasc Res, February 1, 2008; 77(3): 560 - 569. [Abstract] [Full Text] [PDF]

				B. Wang, R. C. Scott, C. B. Pattillo, B. Prabhakarpandian, S. Sundaram, and M. F. Kiani Microvascular transport model predicts oxygenation changes in the infarcted heart after treatment Am J Physiol Heart Circ Physiol, December 1, 2007; 293(6): H3732 - H3739. [Abstract] [Full Text] [PDF]

				E. Messadi-Laribi, V. Griol-Charhbili, A. Pizard, M.-P. Vincent, D. Heudes, P. Meneton, F. Alhenc-Gelas, and C. Richer Tissue Kallikrein Is Involved in the Cardioprotective Effect of AT1-Receptor Blockade in Acute Myocardial Ischemia J. Pharmacol. Exp. Ther., October 1, 2007; 323(1): 210 - 216. [Abstract] [Full Text] [PDF]

				F. Pinaud, A. Bocquet, O. Dumont, K. Retailleau, C. Baufreton, R. Andriantsitohaina, L. Loufrani, and D. Henrion Paradoxical Role of Angiotensin II Type 2 Receptors in Resistance Arteries of Old Rats Hypertension, July 1, 2007; 50(1): 96 - 102. [Abstract] [Full Text] [PDF]

				M. H. Strauss and A. S. Hall Angiotensin Receptor Blockers May Increase Risk of Myocardial Infarction: Unraveling the ARB-MI Paradox Circulation, August 22, 2006; 114(8): 838 - 854. [Full Text] [PDF]

				R. T. Tsuyuki and M. A. McDonald Response to Tsuyuki and McDonald Circulation, August 22, 2006; 114(8): 855 - 860. [Full Text] [PDF]

				M. Paul, A. Poyan Mehr, and R. Kreutz Physiology of local Renin-Angiotensin systems. Physiol Rev, July 1, 2006; 86(3): 747 - 803. [Abstract] [Full Text] [PDF]

				A. Ichihara, F. Suzuki, T. Nakagawa, Y. Kaneshiro, T. Takemitsu, M. Sakoda, A.H.M. N. Nabi, A. Nishiyama, T. Sugaya, M. Hayashi, et al. Prorenin Receptor Blockade Inhibits Development of Glomerulosclerosis in Diabetic Angiotensin II Type 1a Receptor-Deficient Mice J. Am. Soc. Nephrol., July 1, 2006; 17(7): 1950 - 1961. [Abstract] [Full Text] [PDF]

				S. Helske, S. Syvaranta, M. Kupari, J. Lappalainen, M. Laine, J. Lommi, H. Turto, M. Mayranpaa, K. Werkkala, P. T. Kovanen, et al. Possible role for mast cell-derived cathepsin G in the adverse remodelling of stenotic aortic valves Eur. Heart J., June 2, 2006; 27(12): 1495 - 1504. [Abstract] [Full Text] [PDF]

				M. Volpe, G. Tocci, and C. Savoia Angiotensin II receptor blockers and coronary artery disease: 'presumed innocents' Eur. Heart J., June 2, 2006; 27(12): 1506 - 1507. [Full Text] [PDF]

				L. M C. S M Leao, M. P. C Duarte, D. M. B Silva, P. R. V Bahia, C. M. Coeli, and M. L. F. de Farias Influence of methyltestosterone postmenopausal therapy on plasma lipids, inflammatory factors, glucose metabolism and visceral fat: a randomized study Eur. J. Endocrinol., January 1, 2006; 154(1): 131 - 139. [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]

				P. Verdecchia, F. Angeli, R. Gattobigio, and G. P. Reboldi Do angiotensin II receptor blockers increase the risk of myocardial infarction? Eur. Heart J., November 2, 2005; 26(22): 2381 - 2386. [Abstract] [Full Text] [PDF]

				M. H. Strauss, E. M. Lonn, and S. Verma Is the jury out? Class specific differences on coronary outcomes with ACE-inhibitors and ARBs: insight from meta-analysis and The Blood Pressure Lowering Treatment Trialists' Collaboration Eur. Heart J., November 2, 2005; 26(22): 2351 - 2353. [Full Text] [PDF]

				M. A McDonald, S. H Simpson, J. A Ezekowitz, G. Gyenes, and R. T Tsuyuki Angiotensin receptor blockers and risk of myocardial infarction: systematic review BMJ, October 15, 2005; 331(7521): 873. [Abstract] [Full Text] [PDF]

				Z. R Yousef, F. Leyva, and C. Gibbs Angiotensin receptor blockers and myocardial infarction: Cautions voiced are biologically credible BMJ, May 28, 2005; 330(7502): 1270 - 1270. [Full Text]

				T. L Ripley Valsartan in Chronic Heart Failure Ann. Pharmacother., March 1, 2005; 39(3): 460 - 469. [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]

				S. Verma and M. Strauss Angiotensin receptor blockers and myocardial infarction BMJ, November 27, 2004; 329(7477): 1248 - 1249. [Full Text] [PDF]

				E. L. Schiffrin and R. M. Touyz From bedside to bench to bedside: role of renin-angiotensin-aldosterone system in remodeling of resistance arteries in hypertension Am J Physiol Heart Circ Physiol, August 1, 2004; 287(2): H435 - H446. [Full Text] [PDF]