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Trans-resveratrol simultaneously increases cytoplasmic Ca2+ levels and nitric oxide release in human endothelial cells

✍ Scribed by Jacobo Elíes; Andrea Cuíñas; Verónica García-Morales; Francisco Orallo; Manuel Campos-Toimil


Publisher
John Wiley and Sons
Year
2011
Tongue
English
Weight
387 KB
Volume
55
Category
Article
ISSN
1613-4125

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✦ Synopsis


Abstract

Scope: The aim of this study was to investigate whether the dietary polyphenol trans‐resveratrol (t‐Resv) increases [Ca^2+^]~c~ in endothelial cells, leading to a simultaneous augmentation of nitric oxide (NO) biosynthesis.

Methods and results: We have separately and simultaneously measured [Ca^2+^]~c~ and NO in human endothelial cells using the Ca^2+^ indicator fura‐2 and the NO‐sensitive fluorescent probe 4,5‐diaminofluorescein. In ∼30% of cells, t‐Resv (30 μM) induced an increase in [Ca^2+^]~c~ with a transient as well as sustained component and a simultaneous increase in NO biosynthesis. This effect was reduced by non‐selective Ca^2+^ channel blockers, inhibition of intracellular Ca^2+^ 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 Ca^2+^ 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 [Ca^2+^]~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.