on April 29, 2002
Circulation. 2002
Published online before print April 29, 2002, doi: 10.1161/01.CIR.0000016049.86468.23
Published online before print April 29, 2002, doi: 10.1161/01.CIR.0000016049.86468.23
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Submitted on December 28, 2001
From the Canadian Institutes of Health Research Multidisciplinary Research Group on Hypertension (Q.N.D., M.E.M., A.V., M.F.N., F.A., E.L.S.), Hyperlipidemia and Atherosclerosis Research Group (J.S.C.), Clinical Research Institute of Montreal, Montreal, Quebec, Canada; and Regensburg University Clinic (D.E.), Regensburg, Germany. * To whom correspondence should be addressed. E-mail: schiffe{at}ircm.qc.ca.
Background—Pioglitazone and rosiglitazone, thiazolidinedione peroxisome proliferator--activated receptor- Methods and Results—Sprague-Dawley rats received Ang II (120 ng · kg-1 · min-1 SC) with or without pioglitazone (10 mg · kg-1 · d-1) or rosiglitazone (5 mg · kg-1 · d-1) for 7 days. Systolic BP, elevated in Ang II--infused rats (176±5 mm Hg) versus controls (109±2 mm Hg, P<0.01), was reduced by pioglitazone (134±2 mm Hg) or rosiglitazone (123±2 mm Hg). In mesenteric small arteries studied in a pressurized myograph, media/lumen ratio was increased (P<0.05) and acetylcholine-induced relaxation impaired in Ang II--infused rats (P<0.05); both were normalized by the thiazolidinediones. In Ang II--infused rats, vascular DNA synthesis (by 3H-thymidine incorporation); expression of cell cycle proteins cyclin D1 and cdk4, angiotensin II type 1 receptors, vascular cell adhesion molecule-1, and platelet and endothelial cell adhesion molecule; and nuclear factor- Conclusions—Thiazolidinedione PPAR-
Revised on February 21, 2002
Accepted on February 21, 2002
Structure, Endothelial
Function, Cell Growth, and Inflammation in Blood Vessels of
Angiotensin II--Infused Rats. Role of Peroxisome
Proliferator--Activated Receptor-
Quy N. Diep MSc Pharm, PhD, 
(PPAR) activators, reduce blood pressure (BP) in some hypertensive models by unclear mechanisms. We tested the hypothesis that pioglitazone or rosiglitazone would prevent BP elevation and vascular dysfunction in angiotensin (Ang) II--infused rats by direct vascular effects.
B activity were increased. These changes were abrogated by pioglitazone or rosiglitazone. activators attenuated the development of hypertension, corrected structural abnormalities, normalized cell growth, and improved endothelial dysfunction induced by Ang II and prevented upregulation of angiotensin II type 1 receptors, cell cycle proteins, and proinflammatory mediators. Thiazolidinediones may be useful in the prevention and/or treatment of hypertension, particularly when it is associated with insulin resistance or diabetes mellitus.
Key words: hypertension • arteries • remodeling • muscle, smooth • inflammation
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