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Keywords:

  • Calcium;
  • Endothelial cells;
  • Imaging;
  • Nitric oxide;
  • Resveratrol

Abstract

Scope: The aim of this study was to investigate whether the dietary polyphenol trans-resveratrol (t-Resv) increases [Ca2+]c in endothelial cells, leading to a simultaneous augmentation of nitric oxide (NO) biosynthesis.

Methods and results: We have separately and simultaneously measured [Ca2+]c and NO in human endothelial cells using the Ca2+ indicator fura-2 and the NO-sensitive fluorescent probe 4,5-diaminofluorescein. In ∼30% of cells, t-Resv (30 μM) induced an increase in [Ca2+]c with a transient as well as sustained component and a simultaneous increase in NO biosynthesis. This effect was reduced by non-selective Ca2+ channel blockers, inhibition of intracellular Ca2+ release, inhibition of endothelial nitric oxide synthase (eNOS) and, to a lesser extent, inhibition of extracellular signal-regulated kinase 1/2 (ERK 1/2) or 5′ adenosine monophosphate-activated protein kinase (AMPK). t-Resv did not modify in vitro eNOS activity, suggesting that the observed stimulation of NO generation proceeds via mobilisation of Ca2+ and not through direct effects on eNOS.

Conclusion: We therefore show, for the first time, that t-Resv induces a concentration-dependent, simultaneous increase in [Ca2+]c and NO biosynthesis that could be linked to its endothelium-dependent vasorelaxant effect. Under the assumption that t-Resv exhibits similar behaviour in human blood vessels in vivo, the pharmacological properties described here may contribute to the beneficial cardiovascular effects of this polyphenol by improving endothelial function.