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 microM) 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.