Resveratrol may attenuate vascular inflammation in aging

Abstract

Aging is associated with pro-inflammatory phenotypic changes in blood vessels, which is likely to contribute to the increased cardiovascular morbidity and decline in organ functions in elderly patients. Resveratrol, a polyphenolic stilbene derivate found in more than 70 plants has been proposed to exert beneficial anti-oxidant and anti-inflammatory effects in cardiovascular disease. In addition, in lower organisms (C. elegans, D. melanogaster) resveratrol exerts anti-aging effects extending the lifespan. To test the hypothesis that resveratrol exerts vasculoprotective effects in mammalian aging we assessed its effects on the function and phenotype of blood vessels of young (Y, 3 month old) and aged (A, 29 month old) F344 rats. Resveratrol (10-5 to 3x10-4 mol/L) elicited concentration-dependent relaxations of mesenteric arterioles and carotid arteries, which were preserved in aging. In vessels of aged rats there was an impaired dilation to acetylcholine (at 3x10-6 mol/L, Y: 89±4%, A: 48±15%) and an increased superoxide production, that were not affected significantly by in vitro administration of resveratrol. Endothelial function was also unaffected in aged rats with in vivo resveratrol treatment (3 mg/kg/day for 1 week). Vascular expression of the inflammatory markers iNOS and ICAM-1 was significantly increased with age and was attenuated by resveratrol treatment (in organoid culture). In vivo resveratrol treatment also decreased expression of inflammatory markers. Thus, we propose that anti-inflammatory action of resveratrol may offer novel anti-aging cardioprotective therapeutic strategies. (Grant support: AHA 0430108N, 0435140N, American Federation for Aging Research, AHAF H2004-024; California Grape Commission).