This Article Full Text Full Text (PDF) Data Supplement All Versions of this Article: 48/5/942    most recent 01.HYP.0000241061.51003.b7v1 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 Barker, T. A. Articles by Berk, B. C. Search for Related Content PubMed PubMed Citation Articles by Barker, T. A. Articles by Berk, B. C. Pubmed/NCBI databases Compound via MeSH Substance via MeSH Hazardous Substances DB AMLODIPINE BESYLATE BENAZEPRIL HYDROCHLORIDE Related Collections Remodeling ACE/Angiotension receptors Smooth muscle proliferation and differentiation Other Vascular biology

(Hypertension. 2006;48:942.)
© 2006 American Heart Association, Inc.

Original Articles

Angiotensin II Type 2 Receptor Expression After Vascular Injury

Differing Effects of Angiotensin-Converting Enzyme Inhibition and Angiotensin Receptor Blockade

Thomas A. Barker; Michael P. Massett; Vyacheslav A. Korshunov; Amy M. Mohan; Amy J. Kennedy; Bradford C. Berk

From the Cardiovascular Research Institute (T.A.B., M.P.M., V.A.K., A.M.M., B.C.B.) and Departments of Medicine and Biostatistics (A.J.K.), University of Rochester, Rochester, NY.

Correspondence to Bradford C. Berk, University of Rochester, Box 679, 601 Elmwood Ave, Rochester, NY 14642. E-mail bradford_berk{at}urmc rochester.edu

It has been suggested that the effects of angiotensin II type 1 receptor (AT₁R) blockers are in part because of angiotensin II type 2 receptor (AT₂R) signaling. Interactions between the AT₂R and kinins modulate cardiovascular function. Because AT₂R expression increases after vascular injury, we hypothesized that the effects on vascular remodeling of the AT₁R blocker valsartan and the ACE inhibitor benazepril require AT₂R signaling through the bradykinin 1 and 2 receptors (B₁R and B₂R). To test this hypothesis, Brown Norway rats were assigned to 8 treatments (n=16): valsartan, valsartan+PD123319 (AT₂R inhibitor), valsartan+des-arg⁹-[Leu⁸]-bradykinin (B₁R inhibitor), valsartan+HOE140 (B₂R inhibitor), benazepril, benazepril+HOE140, amlodipine, and vehicle. After 1 week of treatment, carotid balloon injury was performed. Two weeks later, carotids were harvested for morphometry and analysis of receptor expression by immunohistochemistry and Western blotting. Valsartan and benazepril significantly reduced the intima:media ratio compared with vehicle. Blockade of AT₂R, B₁R, or B₂R in the presence of valsartan prevented the reduction seen with valsartan alone. B₂R blockade inhibited the effect of benazepril. Injury increased AT₁R, AT₂R, B₁R, and B₂R expression. Treatment with valsartan but not benazepril significantly increased intima AT₂R expression 2-fold compared with vehicle, which was not reversed by inhibition of AT₂R, B₁R, and B₂R. Functionally, valsartan increased intimal cGMP levels compared with vehicle, and this increase was inhibited by blocking the AT₂R, B₁R, and B₂R. Results suggest that AT₂R expression and increased cGMP represent a molecular mechanism that differentiates AT₁R blockers, such as valsartan, from angiotensin-converting enzyme inhibitors like benazepril.

Key Words: valsartan • angiotensin • AT₂R • restenosis • rat

This article has been cited by other articles:

				S. Peters, B. Behnisch, T. Heilmann, and C. Richter First-in-man use of polymer-free valsartan-eluting stents in small coronary vessels: a comparison to polymer-free rapamycin (2%)-eluting stents Journal of Renin-Angiotensin-Aldosterone System, June 1, 2009; 10(2): 91 - 95. [Abstract] [PDF]

				K. P. Malabanan, P. Kanellakis, A. Bobik, and L. M. Khachigian Activation Transcription Factor-4 Induced by Fibroblast Growth Factor-2 Regulates Vascular Endothelial Growth Factor-A Transcription in Vascular Smooth Muscle Cells and Mediates Intimal Thickening in Rat Arteries Following Balloon Injury Circ. Res., August 15, 2008; 103(4): 378 - 387. [Abstract] [Full Text] [PDF]

				S. Heeneman, J. C. Sluimer, and M. J.A.P. Daemen Angiotensin-Converting Enzyme and Vascular Remodeling Circ. Res., August 31, 2007; 101(5): 441 - 454. [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]