This Article Full Text Full Text (PDF) All Versions of this Article: 111/8/1006    most recent 01.CIR.0000156503.62815.48v1 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 You, D. Articles by Henrion, D. Search for Related Content PubMed PubMed Citation Articles by You, D. Articles by Henrion, D. Related Collections ACE/Angiotension receptors Animal models of human disease Other hypertension Other Treatment Related Article

(Circulation. 2005;111:1006-1011.)
© 2005 American Heart Association, Inc.

Hypertension

High Blood Pressure Reduction Reverses Angiotensin II Type 2 Receptor–Mediated Vasoconstriction Into Vasodilation in Spontaneously Hypertensive Rats

Dong You, BSc; Laurent Loufrani, PhD; Celine Baron, BSc; Bernard I. Levy, MD, PhD; Robert E. Widdop, PhD; Daniel Henrion, PharmD, PhD

From INSERM Unit 541 (D.Y.) and Department of Physiology (B.I.L.), AP-HP-Hôpital Lariboisière, Paris, France; UMR-CNRS 6188, University of Angers, Angers, France (L.L., C.B., D.H.); and Department of Pharmacology, Monash University, Melbourne, Australia (R.E.W.).

Correspondence to D. Henrion, PharmD, PhD, Laboratoire de Physiologie, UMR-CNRS 6188, Faculté de Médecine, 49045 Angers, France. E-mail daniel.henrion{at}med.univ-angers.fr

Received May 20, 2004; revision received September 28, 2004; accepted November 10, 2004.

Background— We have previously shown that angiotensin II type 2 receptor (AT₂R) stimulation causes endothelium-dependent vasodilation that does not desensitize after chronic angiotensin II type 1 receptor (AT₁R) blockade, suggesting a role for AT₂R in antihypertensive treatment.

Methods and Results— We recorded mean arterial pressure (MAP) and investigated AT₂R by Western blot analysis, immunohistochemistry, and function in isolated mesenteric resistance arteries (205 µm in diameter) from Wistar-Kyoto (WKY) rats and spontaneously hypertensive rats (SHR) receiving the following for 4 weeks in drinking water: placebo, AT₁R blockade (candesartan; 2 mg/kg per day), ACE inhibitor (perindopril; 3 mg/kg per day), nonselective vasodilator (hydralazine; 16 or 24 mg/kg per day), or candesartan plus hydralazine (16 mg/kg per day). In precontracted isolated arteries, AT₂R stimulation (angiotensin II in the presence of candesartan) caused vasodilation in WKY rats (MAP=118 mm Hg) and vasoconstriction in SHR (MAP=183 mm Hg). In SHR treated with candesartan (MAP=146 mm Hg) or hydralazine (16 mg/kg per day; MAP=145 mm Hg), AT₂R-induced contraction was reduced by 50%. In SHR treated with perindopril (MAP=125 mm Hg), AT₂R stimulation induced vasodilation. In SHR treated with hydralazine (24 mg/kg per day; MAP=105 mm Hg) and in SHR treated with hydralazine (16 mg/kg per day) plus candesartan (MAP=102 mm Hg), an AT₂R-mediated vasodilation was restored. Immunochemistry and Western blot analysis showed that AT₂R expression, lower in SHR than in WKY rats, was restored to normal levels by treatments reducing arterial pressure in SHR.

Conclusions— Our results suggest that in resistance arteries of SHR, (1) AT₂R is downregulated by hypertension, and (2) specific and nonspecific antihypertensive treatments restore AT₂R expression and vasodilator functions.

Key Words: angiotensin • receptors • vasculature • vasodilation • hypertension

Related Article:

Influence of Changes of Blood Pressure on Vascular Angiotensin II Receptor Subtype Expression

Anthony M. Heagerty
Circulation 2005 111: 956-957. [Extract] [Full Text]

This article has been cited by other articles:

				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]

				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]

				D. You, L. Waeckel, T. G. Ebrahimian, O. Blanc-Brude, P. Foubert, V. Barateau, M. Duriez, S. LeRicousse-Roussanne, J. Vilar, E. Dejana, et al. Increase in Vascular Permeability and Vasodilation Are Critical for Proangiogenic Effects of Stem Cell Therapy Circulation, July 25, 2006; 114(4): 328 - 338. [Abstract] [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]

				J. Zhou, J. Pavel, M. Macova, Z.-X. Yu, H. Imboden, L. Ge, T. Nishioku, J. Dou, E. Delgiacco, and J. M. Saavedra AT1 Receptor Blockade Regulates the Local Angiotensin II System in Cerebral Microvessels From Spontaneously Hypertensive Rats Stroke, May 1, 2006; 37(5): 1271 - 1276. [Abstract] [Full Text] [PDF]

				J.-M. Vincent, Y. W. Kwan, S. Lung Chan, C. Perrin-Sarrado, J. Atkinson, and J.-M. Chillon Constrictor and Dilator Effects of Angiotensin II on Cerebral Arterioles Stroke, December 1, 2005; 36(12): 2691 - 2695. [Abstract] [Full Text] [PDF]

				A. M. Heagerty Influence of Changes of Blood Pressure on Vascular Angiotensin II Receptor Subtype Expression Circulation, March 1, 2005; 111(8): 956 - 957. [Full Text] [PDF]