Potential pro-inflammatory action of resveratrol in vascular smooth muscle cells from normal and diabetic rats.
OBJECTIVE
Based 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 17beta-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.


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 (0.1-100microM) as well as the structurally related isoflavone genistein (1nM-1microM) 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 E(2) in the culture medium of SMC from normoglycaemic, but not diabetic rats.


CONCLUSIONS
These 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.
Cignarella
Andrea
A
Department of Pharmacological Sciences, University of Milan, via G. Balzaretti 9, I-20133 Milan, Italy. andrea.cignarella@unimi.it
Minici
Claudia
C
Bolego
Chiara
C
Pinna
Christian
C
Sanvito
Paola
P
Gaion
Rosa Maria
RM
Puglisi
Lina
L
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D001011:Aorta / Q000201:enzymology / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004958:Estradiol / Q000494:pharmacology; D019833:Genistein / Q000494:pharmacology; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000201:enzymology*; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011960:Receptors, Estrogen / Q000378:metabolism; D000077185:Resveratrol; D013267:Stilbenes / Q000494:pharmacology*; D046509:Tissue Culture Techniques
D000894:Anti-Inflammatory Agents, Non-Steroidal; D011960:Receptors, Estrogen; D013267:Stilbenes; D004958:Estradiol; D019833:Genistein; D052247:Nitric Oxide Synthase Type II; D000077185:Resveratrol