Potential pro-inflammatory action of resveratrol in vascular smooth muscle cells from normal and diabetic rats

Background and aim: Based on the reported cardioprotective effects of resveratrol, a polyphenotic antioxidant abundant in grapes that binds to estrogen receptors, and the well-characterized anti-inflammatory properties of 17 beta-estradiot, the effects of resveratrot on the functional expression of inflammatory enzymes were assessed in vascular smooth muscle cells (SMC) from normoglycaernic and streptozotocin-diabetic rats. Methods and results: SMC were isolated from the aorta four weeks after treating rats with streptozotocin or its vehicle. In SMC exposed to a cytokine mixture for 24h, unexpectedly, treatment with resveratrol (0.1-100 mu M) as well as the structurally related isoflavone genistein (1 nM-1 mu M) enhanced expression of inducible NO synthase (iNOS). Genistein failed to mimic the elevated iNOS activity induced by resveratrol. Inhibition of estrogen receptors by the pure antiestrogen ICI 182,780 reversed the action of resveratrol on NOS. In addition, resveratrol failed to alter cyclooxygenase-2 protein levels but reduced the accumulation of prostaglandin E-2 in the culture medium of SMC from normogtycaemic, but not diabetic rats. Conclusions: These results indicate that resveratrot, at concentrations approaching putative peak plasma levels in vivo, exhibited no anti-inflammatory properties in vascular SMC from normal and diabetic rats. By contrast, resveratrot displayed a potential pro-inflammatory activity in settings of vascular inflammation. (c) 2005 Elsevier B.V. All rights reserved.