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Hypertension. 2002;40:866-871
Published online before print October 14, 2002, doi: 10.1161/01.HYP.0000037969.41360.CC
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(Hypertension. 2002;40:866.)
© 2002 American Heart Association, Inc.

Scientific Contributions

PPAR{alpha} Activator Effects on Ang II–Induced Vascular Oxidative Stress and Inflammation

Quy N. Diep; Farhad Amiri; Rhian M. Touyz; Jeffrey S. Cohn; Dierk Endemann; Mario Fritsch Neves; Ernesto L. Schiffrin

From the CIHR Multidisciplinary Research Group on Hypertension (Q.N.D., F.A., R.M.T., M.F.N., E.L.S.) and the Hyperlipidemia and Atherosclerosis Research Group (J.S.C.), Clinical Research Institute of Montreal, Montreal, Quebec, Canada; and Regensburg University Clinic (D.E.), Regensburg, Germany.

Correspondence to Ernesto L. Schiffrin, MD, PhD, FRCPC, Clinical Research Institute of Montreal, 110 Pine Avenue West, Montreal, Quebec, Canada H2W 1R7. E-mail schiffe{at}ircm.qc.ca

Docosahexaenoic acid (DHA), a peroxisome proliferator–activated receptor-{alpha} (PPAR{alpha}) activator, reduces blood pressure (BP) in some hypertensive models by unclear mechanisms. We tested the hypothesis that DHA would prevent BP elevation and improve vascular dysfunction in angiotensin (Ang) II–infused rats by modulating of NADPH oxidase activity and inflammation in vascular wall. Sprague-Dawley rats received Ang II (120 ng/kg per minute SC) with or without DHA (2.5 mL of oil containing 40% DHA/d PO) for 7 days. Systolic BP (mm Hg), elevated in Ang II–infused rats (172±3) versus controls (108±2, P<0.01), was reduced by DHA (112±4). 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 DHA. In blood vessels of Ang II–infused rats, NADPH oxidase activity measured by chemiluminescence and expression of adhesion molecules intercellular adhesion molecule and vascular cell adhesion molecule-1 were significantly increased. These changes were abrogated by DHA. PPAR{alpha} activator DHA attenuated the development of hypertension, corrected structural abnormalities, and improved endothelial dysfunction induced by Ang II. These effects are associated with decreased oxidative stress and inflammation in the vascular wall.


Key Words: hypertension, experimental • resistance • remodeling • muscle, smooth, vascular • free radicals




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