This Article Full Text Full Text (PDF) All Versions of this Article: 45/5/840    most recent 01.HYP.0000159192.93968.8fv1 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 Carey, R. M. Search for Related Content PubMed PubMed Citation Articles by Carey, R. M. Related Collections ACE/Angiotension receptors

(Hypertension. 2005;45:840.)
© 2005 American Heart Association, Inc.

Hypertension Highlights

Cardiovascular and Renal Regulation by the Angiotensin Type 2 Receptor

The AT₂ Receptor Comes of Age

From the Division of Endocrinology and Metabolism, Department of Medicine, University of Virginia School of Medicine, Charlottesville.

Correspondence to Dr Robert M. Carey, P.O. Box 801414, UVA Health System, Charlottesville, VA 22908. E-mail rmc4c@virginia.edu

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

	Introduction

 
The renin-angiotensin system is a coordinated hormonal cascade of major importance in cardiovascular and renal regulation. The principle effector of this system is the octapeptide angiotensin II (Ang II), which acts at 2 cell membrane receptors, AT₁ and AT₂. The majority of the actions of Ang II have been demonstrated to be mediated by the AT₁ receptor, including growth promotion, vasoconstriction, antinatriuresis, aldosterone secretion, salt appetite, thirst, sympathetic outflow and inhibition of renin biosynthesis, and secretion.¹ The AT₂ receptor has been less well understood. Past studies, however, clearly demonstrated that the AT₂ receptor mediates cellular differentiation and growth, opposing the actions of Ang II through the AT₁ receptor.²

Studies in the mid to late 1990s demonstrated that AT₂ receptor stimulation engenders an autacoid vasodilator cascade composed of bradykinin (BK), nitric oxide (NO), and guanosine cyclic 3', 5'-monophosphate (cGMP).^3–5 This discovery turned attention to the possibility that the AT₂ receptor may mediate vasodilation, opposing the vasoconstrictor actions of Ang II at the AT₁ receptor.⁶ Parallel cell signaling studies indicated that the AT₂ receptor is G-protein–coupled (through Gi) and that receptor stimulation is accompanied by an increase in phosphotyrosine phosphatase activity and an inhibition of MAP kinase enzymes (p42 and p44) composing the extracellular signal-related kinase (ERK1/2). AT₂ receptor-mediated inhibition of the extracellular signal-regulated kinase pathway opposed the actions of Ang II, resulting in extracellular signal-regulated kinase phosphorylation via the AT₁ receptor.^1,2,6,7

Work during the late 1990s through 2002 suggested that the AT₂ receptor might serve as a vasodilator counterforce . . . [Full Text of this Article]

This article has been cited by other articles:

				A. P. Mecca, T. E. O'Connor, M. J. Katovich, and C. Sumners Candesartan pretreatment is cerebroprotective in a rat model of endothelin-1-induced middle cerebral artery occlusion Exp Physiol, August 1, 2009; 94(8): 937 - 946. [Abstract] [Full Text] [PDF]

				L. Yvan-Charvet, F. Massiera, N. Lamande, G. Ailhaud, M. Teboul, N. Moustaid-Moussa, J.-M. Gasc, and A. Quignard-Boulange Deficiency of Angiotensin Type 2 Receptor Rescues Obesity But Not Hypertension Induced by Overexpression of Angiotensinogen in Adipose Tissue Endocrinology, March 1, 2009; 150(3): 1421 - 1428. [Abstract] [Full Text] [PDF]

				B. Ulmasov, Z. Xu, L. H. Tetri, T. Inagami, and B. A. Neuschwander-Tetri Protective role of angiotensin II type 2 receptor signaling in a mouse model of pancreatic fibrosis Am J Physiol Gastrointest Liver Physiol, February 1, 2009; 296(2): G284 - G294. [Abstract] [Full Text] [PDF]

				N. E. Hoch, T. J. Guzik, W. Chen, T. Deans, S. A. Maalouf, P. Gratze, C. Weyand, and D. G. Harrison Regulation of T-cell function by endogenously produced angiotensin II Am J Physiol Regulatory Integrative Comp Physiol, February 1, 2009; 296(2): R208 - R216. [Abstract] [Full Text] [PDF]

				L. E. Yang, M. B. Sandberg, A. D. Can, K. Pihakaski-Maunsbach, and A. A. McDonough Effects of dietary salt on renal Na+ transporter subcellular distribution, abundance, and phosphorylation status Am J Physiol Renal Physiol, October 1, 2008; 295(4): F1003 - F1016. [Abstract] [Full Text] [PDF]

				H. Ohtsu, S. Higuchi, H. Shirai, K. Eguchi, H. Suzuki, A. Hinoki, E. Brailoiu, A. D. Eckhart, G. D. Frank, and S. Eguchi Central Role of Gq in the Hypertrophic Signal Transduction of Angiotensin II in Vascular Smooth Muscle Cells Endocrinology, July 1, 2008; 149(7): 3569 - 3575. [Abstract] [Full Text] [PDF]

				K. Thieme, D. M. N. Eguti, M. Mello-Aires, and M. Oliveira-Souza The effect of angiotensin II on intracellular pH is mediated by AT1 receptor translocation Am J Physiol Cell Physiol, July 1, 2008; 295(1): C138 - C145. [Abstract] [Full Text] [PDF]

				J. H. Lee, S. Xia, and L. Ragolia Upregulation of AT2 receptor and iNOS impairs angiotensin II-induced contraction without endothelium influence in young normotensive diabetic rats Am J Physiol Regulatory Integrative Comp Physiol, July 1, 2008; 295(1): R144 - R154. [Abstract] [Full Text] [PDF]

				S. Eguchi Triple Twist Theory of Rho Inhibition by the Angiotensin II Type 2 Receptor Circ. Res., May 23, 2008; 102(10): 1143 - 1145. [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]

				H. Nakashima, G. D. Frank, H. Shirai, A. Hinoki, S. Higuchi, H. Ohtsu, K. Eguchi, A. Sanjay, M. E. Reyland, P. J. Dempsey, et al. Novel Role of Protein Kinase C-{delta} Tyr311 Phosphorylation in Vascular Smooth Muscle Cell Hypertrophy by Angiotensin II Hypertension, February 1, 2008; 51(2): 232 - 238. [Abstract] [Full Text] [PDF]

				C. Roberge, A. C. Carpentier, M.-F. Langlois, J.-P. Baillargeon, J.-L. Ardilouze, P. Maheux, and N. Gallo-Payet Adrenocortical dysregulation as a major player in insulin resistance and onset of obesity Am J Physiol Endocrinol Metab, December 1, 2007; 293(6): E1465 - E1478. [Abstract] [Full Text] [PDF]

				Kai Chen, D. C. Merrill, and J. C. Rose The Importance of Angiotensin II Subtype Receptors for Blood Pressure Control During Mouse Pregnancy Reproductive Sciences, October 1, 2007; 14(7): 694 - 704. [Abstract] [PDF]

				M. C. Chappell Emerging Evidence for a Functional Angiotensin-Converting Enzyme 2-Angiotensin-(1-7)-Mas Receptor Axis: More Than Regulation of Blood Pressure? Hypertension, October 1, 2007; 50(4): 596 - 599. [Full Text] [PDF]

				J. S. Smeda and J. J. McGuire Effects of Poststroke Losartan Versus Captopril Treatment on Myogenic and Endothelial Function in the Cerebrovasculature of SHRsp Stroke, May 1, 2007; 38(5): 1590 - 1596. [Abstract] [Full Text] [PDF]

				L. Oliveira, C. M. Costa-Neto, C. R. Nakaie, S. Schreier, S. I. Shimuta, and A. C. M. Paiva The Angiotensin II AT1 Receptor Structure-Activity Correlations in the Light of Rhodopsin Structure Physiol Rev, April 1, 2007; 87(2): 565 - 592. [Abstract] [Full Text] [PDF]

				I. Hernandez Schulman, M.-S. Zhou, and L. Raij Cross-Talk Between Angiotensin II Receptor Types 1 and 2: Potential Role in Vascular Remodeling in Humans Hypertension, February 1, 2007; 49(2): 270 - 271. [Full Text] [PDF]

				L. J. Salomone, N. L. Howell, H. E. McGrath, B. A. Kemp, S. R. Keller, J. J. Gildea, R. A. Felder, and R. M. Carey Intrarenal Dopamine D1-Like Receptor Stimulation Induces Natriuresis via an Angiotensin Type-2 Receptor Mechanism Hypertension, January 1, 2007; 49(1): 155 - 161. [Abstract] [Full Text] [PDF]

				H. Suzuki, K. Eguchi, H. Ohtsu, S. Higuchi, S. Dhobale, G. D. Frank, E. D. Motley, and S. Eguchi Activation of Endothelial Nitric Oxide Synthase by the Angiotensin II Type 1 Receptor Endocrinology, December 1, 2006; 147(12): 5914 - 5920. [Abstract] [Full Text] [PDF]

				R. M. Carey and J. Park Role of Angiotensin Type 2 Receptors in Vasodilation of Resistance and Capacitance Vessels Hypertension, November 1, 2006; 48(5): 824 - 825. [Full Text] [PDF]

				M.-Z. Zhang, B. Yao, H.-F. Cheng, S.-W. Wang, T. Inagami, and R. C. Harris Renal cortical cyclooxygenase 2 expression is differentially regulated by angiotensin II AT1 and AT2 receptors PNAS, October 24, 2006; 103(43): 16045 - 16050. [Abstract] [Full Text] [PDF]

				H. Beaudry, L. Gendron, M.-O. Guimond, M. D. Payet, and N. Gallo-Payet Involvement of Protein Kinase C{alpha} (PKC{alpha}) in the Early Action of Angiotensin II Type 2 (AT2) Effects on Neurite Outgrowth in NG108-15 Cells: AT2-Receptor Inhibits PKC{alpha} and p21ras Activity Endocrinology, September 1, 2006; 147(9): 4263 - 4272. [Abstract] [Full Text] [PDF]

				N. Poulter, A. D Hughes, B. Williams, A. J. Brady, and G. McInnes Angiotensin-Converting Enzyme Inhibitors Versus Angiotensin Receptor Blockers: A mini-symposium held at the British Hypertension Society Meeting, September 2005 Journal of Renin-Angiotensin-Aldosterone System, June 1, 2006; 7(2): 104 - 121. [PDF]

				S. H. Padia, N. L. Howell, H. M. Siragy, and R. M. Carey Renal Angiotensin Type 2 Receptors Mediate Natriuresis Via Angiotensin III in the Angiotensin II Type 1 Receptor-Blocked Rat Hypertension, March 1, 2006; 47(3): 537 - 544. [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]

				A. P. V. Dantas and K. Sandberg Regulation of ACE2 and ANG-(1-7) in the aorta: new insights into the renin-angiotensin system in the control of vascular function Am J Physiol Heart Circ Physiol, September 1, 2005; 289(3): H980 - H981. [Full Text] [PDF]