Published Online
on December 11, 2006

A more recent version of this article appeared on February 1, 2007

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Submitted on August 21, 2006
Revised on September 8, 2006

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

Carmine Savoia; Rhian M. Touyz; Massimo Volpe; and 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.

^* To whom correspondence should be addressed. E-mail: ernesto.schiffrin{at}mcgill.ca.

Abstract--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 -blocker atenolol. Twenty-six hypertensive type 2 diabetic patients treated with oral hypoglycemic and antihypertensive agents (not receiving angiotensin receptor blockers or -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

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