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

Background and aimBased on the reported cardioprotective effects of resveratrol, a polyphenolic antioxidant abundant in grapes that binds to estrogen receptors, and the well-characterized anti-inflammatory properties of 17β-estradiol, the effects of resveratrol on the functional expression of inflammatory enzymes were assessed in vascular smooth muscle cells (SMC) from normoglycaemic and streptozotocin-diabetic rats.Methods and resultsSMC were isolated from the aorta four weeks after treating rats with streptozotocin or its vehicle. In SMC exposed to a cytokine mixture for 24 h, unexpectedly, treatment with resveratrol (0.1–100 μM) as well as the structurally related isoflavone genistein (1 nM–1 μM) 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 iNOS. In addition, resveratrol failed to alter cyclooxygenase-2 protein levels but reduced the accumulation of prostaglandin E2 in the culture medium of SMC from normoglycaemic, but not diabetic rats.ConclusionsThese results indicate that resveratrol, at concentrations approaching putative peak plasma levels in vivo, exhibited no anti-inflammatory properties in vascular SMC from normal and diabetic rats. By contrast, resveratrol displayed a potential pro-inflammatory activity in settings of vascular inflammation.