Differential effect of resveratrol on nitric oxide production in endothelial F-2 cells

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Abstract

We examined the rapid effect of resveratrol on nitric oxide (NO) production in endothelial F-2 cells. During an incubation period of 10 min, resveratrol at low concentrations (<20 μM) had no effect on NO production, whereas it significantly increased NO production at high concentrations (>50 μM). In contrast, pretreatment with resveratrol at low concentrations caused a significant decrease in vascular endothelial growth factor (VEGF)-stimulated NO production. Resveratrol failed to induce phosphorylation of endothelial NO synthase (eNOS) and VEGF receptor and did not affect autophosphorylation of the VEGF receptor. However, resveratrol markedly suppressed VEGF-induced eNOS phosphorylation. Resveratrol at high concentrations reduced the viability of F-2 cells as determined by 3-(4,5-dimethyl-2-thiazoyl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) and dye exclusion methods. Resveratrol-stimulated NO production was completely abolished by the depletion of extracellular Ca2+. These results indicate that resveratrol stimulates NO production by a Ca 2+-dependent mechanism and reduces VEGF-stimulated NO production by impairing a Ca2+-independent mechanism in endothelial F-2 cells. However, the stimulatory effect of resveratrol may be partly attributed to its cytotoxicity. © 2009 Pharmaceutical Society of Japan.

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Takahashi, S., Uchiyama, T., & Toda, K. I. (2009). Differential effect of resveratrol on nitric oxide production in endothelial F-2 cells. Biological and Pharmaceutical Bulletin, 32(11), 1840–1843. https://doi.org/10.1248/bpb.32.1840

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