This Article Full Text Full Text (PDF) All Versions of this Article: 49/2/341    most recent 01.HYP.0000253968.95136.b8v1 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 Savoia, C. Articles by Schiffrin, E. L. Search for Related Content PubMed PubMed Citation Articles by Savoia, C. Articles by Schiffrin, E. L. Related Collections Clinical Studies Type 2 diabetes ACE/Angiotension receptors Related Article

(Hypertension. 2007;49:341.)
© 2007 American Heart Association, Inc.

Original Articles

Angiotensin Type 2 Receptor in Resistance Arteries of Type 2 Diabetic Hypertensive Patients

Carmine Savoia; Rhian M. Touyz; Massimo Volpe; Ernesto L. Schiffrin

From the Lady Davis Institute for Medical Research (C.S., E.L.S.), Sir Mortimer B. Davis–Jewish General Hospital, McGill University, Montreal, Quebec, Canada; Kidney Research Center (R.M.T.), Ontario Health Research Institute, University of Ottawa, Ottawa, Ontario, Canada; Division of Cardiology (M.V.), 2nd Faculty of Medicine, University "La Sapienza," Ospedale Sant’Andrea and IRCCS Neuromed, Pozzilli, Italy.

Correspondence to Ernesto L. Schiffrin, Department of Medicine, Sir Mortimer B. Davis–Jewish General Hospital, #B-127, 3755 Cote Ste-Catherine Rd, Montreal, Quebec, Canada H3T 1E2. E-mail ernesto.schiffrin{at}mcgill.ca

The role of angiotensin type 2 receptor (AT₂R) on vascular responses to angiotensin II in humans remains unclear. In this study we explored whether AT₂R is expressed and functionally active on peripheral resistance arteries of hypertensive diabetic patients treated for 1 year with either the angiotensin receptor blocker valsartan or the ß-blocker atenolol. Twenty-six hypertensive type 2 diabetic patients treated with oral hypoglycemic and antihypertensive agents (not receiving angiotensin receptor blockers or ß-blockers) were randomly assigned to double-blind treatment for 1 year with valsartan or atenolol once daily added to their previous therapy in a clinical trial that we reported recently and compared with 10 normal subjects. Resistance arteries dissected from gluteal subcutaneous tissues were assessed on a pressurized myograph. Vasomotor response curves to angiotensin II (1 nmol/L to 1 µmol/L) were performed on norepinephrine precontracted vessels in the presence of valsartan (10 µmol/L) with or without the AT₂R inhibitor PD123319 (1 µmol/L). AT₂R expression was evaluated by confocal microscopy. After 1 year of treatment, systolic and diastolic blood pressure was controlled and comparable in the valsartan and atenolol groups. Angiotensin II evoked a significant vasodilatory response only on resistance arteries from patients treated with valsartan, effect blocked by PD123319. AT₂R expression was 4-fold higher in small arteries of valsartan-treated patients. In conclusion, AT₂Rs are upregulated and contribute to angiotensin II–induced vasodilation in resistance arteries of hypertensive diabetic patients treated with angiotensin type 1 receptor blockers and may mediate, in part, vascular actions of these drugs in high cardiovascular risk patients.

Key Words: AT₂ receptor • angiotensin receptors • human hypertension • type 2 diabetes • resistance arteries

Related Article:

Cross-Talk Between Angiotensin II Receptor Types 1 and 2: Potential Role in Vascular Remodeling in Humans

Ivonne Hernandez Schulman, Ming-Sheng Zhou, and Leopoldo Raij
Hypertension 2007 49: 270-271. [Full Text] [PDF]

This article has been cited by other articles:

				C. Schindler ACE-inhibitor, AT1-receptor-antagonist, or both? A clinical pharmacologist`s perspective after publication of the results of ONTARGET Therapeutic Advances in Cardiovascular Disease, August 1, 2008; 2(4): 233 - 248. [Abstract] [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]

				C. Guilluy, M. Rolli-Derkinderen, L. Loufrani, A. Bourge, D. Henrion, L. Sabourin, G. Loirand, and P. Pacaud Ste20-Related Kinase SLK Phosphorylates Ser188 of RhoA to Induce Vasodilation in Response to Angiotensin II Type 2 Receptor Activation Circ. Res., May 23, 2008; 102(10): 1265 - 1274. [Abstract] [Full Text] [PDF]

				M. E Johansson, B. Fagerberg, and G. Bergstrom Angiotensin type 2 receptor is expressed in human atherosclerotic lesions Journal of Renin-Angiotensin-Aldosterone System, March 1, 2008; 9(1): 17 - 21. [Abstract] [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]

				R. M. Carey Angiotensin Receptors and Aging Hypertension, July 1, 2007; 50(1): 33 - 34. [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]