(Hypertension. 1999;33:613-621.)
© 1999 American Heart Association, Inc.
Brief Review |
Recent Progress in Angiotensin II Type 2 Receptor Research in the Cardiovascular System
From the Division of Cardiovascular Research, Department of Medicine, Harvard Medical School, Brigham and Women's Hospital, Boston, Mass.
Correspondence to Masatsugu Horiuchi, MD, PhD, Department of Medical Biochemistry, Ehime University School of Medicine, Shigenobu, Onsen-gun, Ehime 791-0295, Japan. E-mail horiuchi{at}m.ehime-u.ac.jp
Abstract—Angiotensin II (Ang II) plays an important role in regulating cardiovascular hemodynamics and structure. Multiple lines of evidence have suggested the existence of Ang II receptor subtypes, and at least 2 distinct receptor subtypes have been defined on the basis of their differential pharmacological and biochemical properties and designated as type 1 (AT1) and type 2 (AT2) receptors. To date, most of the known effects of Ang II in adult tissues are attributable to the AT1 receptor. Recent cloning of the AT2 receptor contributes to reveal its physiological functions, but many functions of the AT2 receptor are still an enigma. AT1 and AT2 receptors belong to the 7-transmembrane, G protein–coupled receptor family. However, accumulating evidence demonstrates that the function and signaling mechanisms of these receptor subtypes are quite different, and these receptors may exert opposite effects in terms of cell growth and blood pressure regulation. We will review the role of the AT2 receptor in the cardiovascular system and the molecular and cellular mechanisms of AT2 receptor action.
Key Words: angiotensin II • apoptosis • blood vessels • cell growth • heart • receptors • signaling
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L. Wu, M. Iwai, H. Nakagami, R. Chen, J. Suzuki, M. Akishita, M. de Gasparo, and M. Horiuchi Effect of Angiotensin II Type 1 Receptor Blockade on Cardiac Remodeling in Angiotensin II Type 2 Receptor Null Mice Arterioscler. Thromb. Vasc. Biol., January 1, 2002; 22(1): 49 - 54. [Abstract] [Full Text] [PDF]
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Y. Takeda-Matsubara, H. Nakagami, M. Iwai, T.-X. Cui, T. Shiuchi, M. Akishita, C. Nahmias, M. Ito, and M. Horiuchi Estrogen Activates Phosphatases and Antagonizes Growth-Promoting Effect of Angiotensin II Hypertension, January 1, 2002; 39(1): 41 - 45. [Abstract] [Full Text] [PDF]
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J. L. Segar, G. B. Dalshaug, K. A. Bedell, O. M. Smith, and T. D. Scholz Angiotensin II in cardiac pressure-overload hypertrophy in fetal sheep Am J Physiol Regulatory Integrative Comp Physiol, December 1, 2001; 281(6): R2037 - R2047. [Abstract] [Full Text] [PDF]
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R. Shimizu-Hirota, H. Sasamura, M. Mifune, H. Nakaya, M. Kuroda, M. Hayashi, and T. Saruta Regulation of Vascular Proteoglycan Synthesis by Angiotensin II Type 1 and Type 2 Receptors J. Am. Soc. Nephrol., December 1, 2001; 12(12): 2609 - 2615. [Abstract] [Full Text] [PDF]
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C. Berry, R. Touyz, A. F. Dominiczak, R. C. Webb, and D. G. Johns Angiotensin receptors: signaling, vascular pathophysiology, and interactions with ceramide Am J Physiol Heart Circ Physiol, December 1, 2001; 281(6): H2337 - H2365. [Abstract] [Full Text] [PDF]
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L. Wu, M. Iwai, H. Nakagami, Z. Li, R. Chen, J. Suzuki, M. Akishita, M. de Gasparo, and M. Horiuchi Roles of Angiotensin II Type 2 Receptor Stimulation Associated With Selective Angiotensin II Type 1 Receptor Blockade With Valsartan in the Improvement of Inflammation-Induced Vascular Injury Circulation, November 27, 2001; 104(22): 2716 - 2721. [Abstract] [Full Text] [PDF]
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J. St-Louis, B. Sicotte, S. Bedard, and M. Brochu Blockade of Angiotensin Receptor Subtypes in Arcuate Uterine Artery of Pregnant and Postpartum Rats Hypertension, November 1, 2001; 38(5): 1017 - 1023. [Abstract] [Full Text] [PDF]
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S. AbdAlla, H. Lother, A. M. Abdel-tawab, and U. Quitterer The Angiotensin II AT2 Receptor Is an AT1 Receptor Antagonist J. Biol. Chem., October 19, 2001; 276(43): 39721 - 39726. [Abstract] [Full Text] [PDF]
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F. Fiordaliso, A. Leri, D. Cesselli, F. Limana, B. Safai, B. Nadal-Ginard, P. Anversa, and J. Kajstura Hyperglycemia Activates p53 and p53-Regulated Genes Leading to Myocyte Cell Death Diabetes, October 1, 2001; 50(10): 2363 - 2375. [Abstract] [Full Text]
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L. H. Opie and M. N. Sack Enhanced Angiotensin II Activity in Heart Failure : Reevaluation of the Counterregulatory Hypothesis of Receptor Subtypes Circ. Res., April 13, 2001; 88(7): 654 - 658. [Abstract] [Full Text] [PDF]
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A. M Allen, M. E Giles, J. Lee, B. J Oldfield, F. A. Mendelsohn, and M. J McKinley Review: AT1-receptors in the central nervous system Journal of Renin-Angiotensin-Aldosterone System, March 1, 2001; 2(1_suppl): S95 - S101. [PDF]
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T.-X. Cui, H. Nakagami, M. Iwai, Y. Takeda, T. Shiuchi, L. Daviet, C. Nahmias, and M. Horiuchi Pivotal role of tyrosine phosphatase SHP-1 in AT2 receptor-mediated apoptosis in rat fetal vascular smooth muscle cell Cardiovasc Res, March 1, 2001; 49(4): 863 - 871. [Abstract] [Full Text] [PDF]
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M. E El-Sabban, K. A Hassan, A. E Birbari, K. M Bitar, and A. B Bikhazi Angiotensin II binding and extracellular matrix remodelling in a rat model of myocardial infarction Journal of Renin-Angiotensin-Aldosterone System, December 1, 2000; 1(4): 369 - 378. [Abstract] [PDF]
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 R. M. Touyz and E. L. Schiffrin Signal Transduction Mechanisms Mediating the Physiological and Pathophysiological Actions of Angiotensin II in Vascular Smooth Muscle Cells Pharmacol. Rev., December 1, 2000; 52(4): 639 - 672. [Abstract] [Full Text] [PDF]
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S. Ravassa, M. A. Fortuno, A. Gonzalez, B. Lopez, G. Zalba, A. Fortuno, and J. Diez Mechanisms of Increased Susceptibility to Angiotensin II-Induced Apoptosis in Ventricular Cardiomyocytes of Spontaneously Hypertensive Rats Hypertension, December 1, 2000; 36(6): 1065 - 1071. [Abstract] [Full Text] [PDF]
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J. Ibrahim, A. D. Hughes, and P. S. Sever Action of Angiotensin II on DNA Synthesis by Human Saphenous Vein in Organ Culture Hypertension, November 1, 2000; 36(5): 917 - 921. [Abstract] [Full Text] [PDF]
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S. L. Malendowicz, P. V. Ennezat, M. Testa, L. Murray, E. H. Sonnenblick, T. Evans, and T. H. LeJemtel Angiotensin II Receptor Subtypes in the Skeletal Muscle Vasculature of Patients With Severe Congestive Heart Failure Circulation, October 31, 2000; 102(18): 2210 - 2213. [Abstract] [Full Text] [PDF]
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Y. Xu, A. S. Clanachan, and B. I. Jugdutt Enhanced Expression of Angiotensin II Type 2 Receptor, Inositol 1,4,5-Trisphosphate Receptor, and Protein Kinase C{epsilon} During Cardioprotection Induced by Angiotensin II Type 2 Receptor Blockade Hypertension, October 1, 2000; 36(4): 506 - 510. [Abstract] [Full Text] [PDF]
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K. Matrougui, Y. E. G. Eskildsen-Helmond, A. Fiebeler, D. Henrion, B. I. Levy, A. Tedgui, and M. J. Mulvany Angiotensin II Stimulates Extracellular Signal-Regulated Kinase Activity in Intact Pressurized Rat Mesenteric Resistance Arteries Hypertension, October 1, 2000; 36(4): 617 - 621. [Abstract] [Full Text] [PDF]
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M. de Gasparo, K. J. Catt, T. Inagami, J. W. Wright, and Th. Unger International Union of Pharmacology. XXIII. The Angiotensin II Receptors Pharmacol. Rev., September 1, 2000; 52(3): 415 - 472. [Abstract] [Full Text] [PDF]
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 A. Leri, F. Fiordaliso, M. Setoguchi, F. Limana, N. H. Bishopric, J. Kajstura, K. Webster, and P. Anversa Inhibition of p53 Function Prevents Renin-Angiotensin System Activation and Stretch-Mediated Myocyte Apoptosis Am. J. Pathol., September 1, 2000; 157(3): 843 - 857. [Abstract] [Full Text] [PDF]
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 M. I. Oliverio and T. M. Coffman Angiotensin II Receptor Physiology Using Gene Targeting Physiology, August 1, 2000; 15(4): 171 - 175. [Abstract] [Full Text] [PDF]
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T. R. Nurkiewicz and M. A. Boegehold Reinforcement of arteriolar myogenic activity by endogenous ANG II: susceptibility to dietary salt Am J Physiol Heart Circ Physiol, July 1, 2000; 279(1): H269 - H278. [Abstract] [Full Text] [PDF]
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Yi Xu, V. Menon, and B. I Jugdutt Cardioprotection after angiotensin II type 1 blockade involves angiotensin II type 2 receptor expression and activation of protein kinase C-{varepsilon} in acutely reperfused myocardial infarction in the dog: Effect of UP269-6 and losartan on AT1- and AT2-receptor expression and IP3 receptor and PKC{varepsilon} proteins Journal of Renin-Angiotensin-Aldosterone System, June 1, 2000; 1(2): 184 - 195. [Abstract] [PDF]
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