Resveratrol inhibits restenosis in an animal model. - GreenMedInfo Summary
Essential role of ER-alpha-dependent NO production in resveratrol-mediated inhibition of restenosis.
Am J Physiol Heart Circ Physiol. 2010 Nov;299(5):H1451-8. Epub 2010 Aug 13. PMID: 20709862
Department of Pharmacology, Toxicology and Neuroscience, Louisiana State University Health Sciences Center, Shreveport, Louisiana 71103, USA.
Resveratrol (Resv), a red wine polyphenol, is known to exhibit vascular protective effects and reduce vascular smooth muscle cell mitogenesis. Vascular smooth muscle cell proliferation is a critical factor in the pathogenesis of restenosis, the renarrowing of vessels that often occurs after angioplasty and/or stent implantation. Although Resv has been shown to be an estrogen receptor (ER) modulator, the role of the ER in Resv-mediated protection against restenosis has not yet been elucidated in vivo. Therefore, with the use of a mouse carotid artery injury model, our objective was to determine the role of ER in modulating Resv-mediated effects on neointimal hyperplasia. Female wild-type and ER-α(-/-) mice were administered a high-fat diet ± Resv for 2 wk. A carotid artery endothelial denudation procedure was conducted, and the mice were administered a high-fat diet ± Resv for an additional 2 wk. Resv-treated wild-type mice exhibited a dramatic decrease in restenosis, with an increasedarterial nitric oxide (NO) synthase (NOS) activity and NO production. However, in the ER-α(-/-) mice, Resv failed to afford protection and failed to increase NO production, apparently because of a decreased availability of the NOS cofactor tetrahydrobiopterin. To verify the role of NO in Resv-mediated effects, mice were coadministered Resv plus a nonselective NOS inhibitor, N(G)-nitro-l-arginine methyl ester (l-NAME). Cotreatment with l-NAME significantly attenuated the antirestenotic properties of Resv. These data thus suggest that Resv inhibits vascular proliferative responses after injury,predominately through an ER-α-dependent increase in NO production.