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(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
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