RT Journal Article SR Electronic T1 Female Rats Fed a High-Fat Diet Were Associated with Vascular Dysfunction and Cardiac Fibrosis in the Absence of Overt Obesity and Hyperlipidemia: Therapeutic Potential of Resveratrol JF Journal of Pharmacology and Experimental Therapeutics JO J Pharmacol Exp Ther FD American Society for Pharmacology and Experimental Therapeutics SP 961 OP 968 DO 10.1124/jpet.107.135061 VO 325 IS 3 A1 Marie-Claude Aubin A1 Claude Lajoie A1 Robert Clément A1 Hugues Gosselin A1 Angelino Calderone A1 Louis P. Perrault YR 2008 UL http://jpet.aspetjournals.org/content/325/3/961.abstract AB It remains presently unknown whether vascular reactivity is impaired and whether maladaptive cardiac remodeling occurs before the onset of overt obesity and in the absence of hyperlipidemia. Normal female rats were fed a high-fat diet for 8 weeks and were associated with a modest nonsignificant increase of body weight (standard diet, 300 ± 10, versus high-fat diet, 329 ± 14 g) and a normal plasma lipid profile. In rats fed a high-fat diet, systolic (171 ± 7 mm Hg) and diastolic blood pressures (109 ± 3) were increased compared to a standard diet (systolic blood pressure, 134 ± 8; diastolic blood pressure, 96 ± 5 mm Hg), and acetylcholine-dependent relaxation of isolated aortic rings (high-fat diet, 22 ± 5%, versus standard diet, 53 ± 8%) was significantly reduced. Furthermore, perivascular fibrosis was detected in the heart of rats fed a high-fat diet. The exogenous addition of resveratrol (trans-3,5,4′-trihydroxystilbene) (0.1 μM) to aortic rings isolated from rats fed a high-fat diet restored acetylcholine-mediated relaxation (47 ± 9%). The administration of resveratrol (20 mg/kg/day for 8 weeks) to rats fed a high-fat diet prevented the increase in blood pressure and preserved acetylcholine-dependent relaxation of isolated aortic rings. However, resveratrol therapy failed to attenuate the perivascular fibrotic response. These data have demonstrated that a high-fat diet fed to normal female rats can elicit a hypertensive response and induce perivascular fibrosis before the development of overt obesity and in the absence of hyperlipidemia. Resveratrol therapy can prevent the hypertensive response in female rats fed a high-fat diet but is without effect on the progression of perivascular fibrosis. The American Society for Pharmacology and Experimental Therapeutics