In memoriam of Dr. Francisco Orallo.
Trans-resveratrol simultaneously increases cytoplasmic Ca2+ levels and nitric oxide release in human endothelial cells
Article first published online: 28 JUN 2011
Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
Molecular Nutrition & Food Research
Special Issue: Resveratrol – Current Status and Outlook
Volume 55, Issue 8, pages 1237–1248, August 2011
How to Cite
Elíes, J., Cuíñas, A., García-Morales, V., Orallo, F. and Campos-Toimil, M. (2011), Trans-resveratrol simultaneously increases cytoplasmic Ca2+ levels and nitric oxide release in human endothelial cells. Mol. Nutr. Food Res., 55: 1237–1248. doi: 10.1002/mnfr.201100240
- Issue published online: 3 AUG 2011
- Article first published online: 28 JUN 2011
- Manuscript Accepted: 16 MAY 2011
- Manuscript Revised: 12 MAY 2011
- Manuscript Received: 6 APR 2011
- Ministerio de Ciencia e Innovación, Spain. Grant Number: SAF2010-22051
- Xunta de Galicia, Spain. Grant Numbers: INCITE08PXIB203092PR, 08CSA019203PR
- FPU pre-doctoral scholarship from the Ministerio de Educación, Spain
- Endothelial cells;
- Nitric oxide;
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.