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Submitted on June 7, 2002
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. * To whom correspondence should be addressed. E-mail: schiffe{at}ircm.qc.ca.
AbstractDocosahexaenoic acid (DHA), a peroxisome proliferator-activated receptor-
Revised on June 26, 2002
PPAR
Quy N. Diep;
Activator Effects on Ang II-Induced Vascular Oxidative Stress and Inflammation
(PPAR
) 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
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.
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