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 Cao, Z. Articles by Cooper, M. E. Search for Related Content PubMed PubMed Citation Articles by Cao, Z. Articles by Cooper, M. E. Related Collections Animal models of human disease Hypertension - basic studies Smooth muscle proliferation and differentiation Receptor pharmacology

(Hypertension. 1999;34:408-414.)
© 1999 American Heart Association, Inc.

Scientific Contributions

Role of Angiotensin Receptor Subtypes in Mesenteric Vascular Proliferation and Hypertrophy

Zemin Cao; Rachael Dean; Leonard Wu; David Casley; Mark E. Cooper

From the Department of Medicine, University of Melbourne, Austin & Repatriation Medical Centre (Repatriation Campus), Heidelberg West, Victoria, Australia.

Abstract—The aim of this study was to explore the regulation of angiotensin receptors after chronic infusion with angiotensin II (Ang II) and to clarify the relative roles of the angiotensin type 1 (AT₁) and type 2 (AT₂) receptors in the mediation of Ang II–induced mesenteric vascular hypertrophy. In male Sprague-Dawley rats, Ang II infusion at a dose of 58.3 ng/min by subcutaneous osmotic minipumps for 14 days led to increased mesenteric weight and wall:lumen ratio of the vessels and proliferation of smooth muscle cells. These vascular changes were attenuated by either valsartan, an AT₁ receptor antagonist, at a dose of 30 mg · kg^-1 · d^-1 by gavage, or PD123319, an AT₂ receptor antagonist, at a dose of 830 ng/min by intraperitoneally implanted osmotic minipumps. Ang II infusion was associated with hypertension, which was prevented by valsartan, but not PD123319. ¹²⁵I-Sar¹, Ile⁸ Ang II binding to mesenteric vasculature was increased after Ang II infusion. Valsartan treatment was associated with reduced Ang II binding to both receptor subtypes, whereas PD123319 was associated with reduced Ang II binding to only the AT₂ receptor subtype. These findings suggest that the trophic and proliferative effects of Ang II on the mesenteric vasculature are mediated by both AT₁ and AT₂ receptors.

Key Words: angiotensin II • receptors, angiotensin • vascular proliferation • proliferating cell nuclear antigen

This article has been cited by other articles:

				A. Seed, R. Gardner, J. McMurray, C. Hillier, D. Murdoch, R. MacFadyen, A. Bobillier, J. Mann, and T. McDonagh Neurohumoral effects of the new orally active renin inhibitor, aliskiren, in chronic heart failure Eur J Heart Fail, November 1, 2007; 9(11): 1120 - 1127. [Abstract] [Full Text] [PDF]

				V. C. Munk, L. Sanchez de Miguel, M. Petrimpol, N. Butz, A. Banfi, U. Eriksson, L. Hein, R. Humar, and E. J. Battegay Angiotensin II Induces Angiogenesis in the Hypoxic Adult Mouse Heart In Vitro Through an AT2-B2 Receptor Pathway Hypertension, May 1, 2007; 49(5): 1178 - 1185. [Abstract] [Full Text] [PDF]

				P. Brassard, F. Amiri, and E. L. Schiffrin Combined Angiotensin II Type 1 and Type 2 Receptor Blockade on Vascular Remodeling and Matrix Metalloproteinases in Resistance Arteries Hypertension, September 1, 2005; 46(3): 598 - 606. [Abstract] [Full Text] [PDF]

				S. Sarlos and J. L. Wilkinson-Berka The Renin-Angiotensin System and the Developing Retinal Vasculature Invest. Ophthalmol. Vis. Sci., March 1, 2005; 46(3): 1069 - 1077. [Abstract] [Full Text] [PDF]

				D. Perlegas, H. Xie, S. Sinha, A. V. Somlyo, and G. K. Owens ANG II type 2 receptor regulates smooth muscle growth and force generation in late fetal mouse development Am J Physiol Heart Circ Physiol, January 1, 2005; 288(1): H96 - H102. [Abstract] [Full Text] [PDF]

				K. Savary, A. Michaud, J. Favier, E. Larger, P. Corvol, and J.-M. Gasc Role of the renin-angiotensin system in primitive erythropoiesis in the chick embryo Blood, January 1, 2005; 105(1): 103 - 110. [Abstract] [Full Text] [PDF]

				M. E. Mabrouk, Q. N. Diep, K. Benkirane, R. M. Touyz, and E. L. Schiffrin SAM68: a downstream target of angiotensin II signaling in vascular smooth muscle cells in genetic hypertension Am J Physiol Heart Circ Physiol, May 1, 2004; 286(5): H1954 - H1962. [Abstract] [Full Text] [PDF]

				R. Candido, T. J. Allen, M. Lassila, Z. Cao, V. Thallas, M. E. Cooper, and K. A. Jandeleit-Dahm Irbesartan but Not Amlodipine Suppresses Diabetes-Associated Atherosclerosis Circulation, March 30, 2004; 109(12): 1536 - 1542. [Abstract] [Full Text] [PDF]

				X. Zhang, M. Lassila, M. E. Cooper, and Z. Cao Retinal Expression of Vascular Endothelial Growth Factor Is Mediated by Angiotensin Type 1 and Type 2 Receptors Hypertension, February 1, 2004; 43(2): 276 - 281. [Abstract] [Full Text] [PDF]

				B. I. Levy Can Angiotensin II Type 2 Receptors Have Deleterious Effects in Cardiovascular Disease?: Implications for Therapeutic Blockade of the Renin-Angiotensin System Circulation, January 6, 2004; 109(1): 8 - 13. [Full Text] [PDF]

				B. Rizkalla, J. M. Forbes, M. E. Cooper, and Z. Cao Increased Renal Vascular Endothelial Growth Factor and Angiopoietins by Angiotensin II Infusion Is Mediated by Both AT1 and AT2 Receptors J. Am. Soc. Nephrol., December 1, 2003; 14(12): 3061 - 3071. [Abstract] [Full Text] [PDF]

				S. Sarlos, B. Rizkalla, C. J. Moravski, Z. Cao, M. E. Cooper, and J. L. Wilkinson-Berka Retinal Angiogenesis Is Mediated by an Interaction between the Angiotensin Type 2 Receptor, VEGF, and Angiopoietin Am. J. Pathol., September 1, 2003; 163(3): 879 - 887. [Abstract] [Full Text] [PDF]

				Z. Cao, F. Bonnet, R. Candido, S. P. Nesteroff, W. C. Burns, H. Kawachi, F. Shimizu, R. M. Carey, M. de Gasparo, and M. E. Cooper Angiotensin Type 2 Receptor Antagonism Confers Renal Protection in a Rat Model of Progressive Renal Injury J. Am. Soc. Nephrol., July 1, 2002; 13(7): 1773 - 1787. [Abstract] [Full Text] [PDF]

				M. Naruse, A. Tanabe, A. Sato, S. Takagi, K. Tsuchiya, T. Imaki, and K. Takano Aldosterone Breakthrough During Angiotensin II Receptor Antagonist Therapy in Stroke-Prone Spontaneously Hypertensive Rats Hypertension, July 1, 2002; 40(1): 28 - 33. [Abstract] [Full Text] [PDF]

				S. Phoon and L. G. Howes Forearm vasodilator response to angiotensin II in elderly women receiving candesartan: role of AT2- receptors Journal of Renin-Angiotensin-Aldosterone System, March 1, 2002; 3(1): 36 - 39. [Abstract] [PDF]

				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]

				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]

				M. El Mabrouk, R. M. Touyz, and E. L. Schiffrin Differential ANG II-induced growth activation pathways in mesenteric artery smooth muscle cells from SHR Am J Physiol Heart Circ Physiol, July 1, 2001; 281(1): H30 - H39. [Abstract] [Full Text] [PDF]

				M. Burnier Angiotensin II Type 1 Receptor Blockers Circulation, February 13, 2001; 103(6): 904 - 912. [Full Text] [PDF]

				M. Mifune, H. Sasamura, R. Shimizu-Hirota, H. Miyazaki, and T. Saruta Angiotensin II Type 2 Receptors Stimulate Collagen Synthesis in Cultured Vascular Smooth Muscle Cells Hypertension, November 1, 2000; 36(5): 845 - 850. [Abstract] [Full Text] [PDF]

				C. Chassagne, C. Adamy, P. Ratajczak, B. Gingras, E. Teiger, E. Planus, P. Oliviero, L. Rappaport, J.-L. Samuel, and S. Meloche Angiotensin II AT2 receptor inhibits smooth muscle cell migration via fibronectin cell production and binding Am J Physiol Cell Physiol, April 1, 2002; 282(4): C654 - C664. [Abstract] [Full Text] [PDF]