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Antioxidants and endothelial nitric oxide synthesis

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Abstract

Oxidative stress in the vasculature has been suggested to contribute to the development of endothelial dysfunction via different mechanisms including LDL oxidation, nitric oxide (NO) scavenging, or oxidation of tetrahydrobiopterin, a critical cofactor of endothelial NO synthase (eNOS). Antioxidants may interfere with these processes and protect NO formed in the endothelium. In particular, ascorbic acid at high concentrations seems to be a prerequisite for sufficient NO bioavailability. Moreover, there is accumulating evidence that ascorbic acid improves tetrahydrobiopterin availability in the vasculature most probably via recycling oxidized tetrahydrobiopterin back to the fully reduced pterin. In addition, ascorbic acid may reduce the α-tocopheroxyl radical and may be required for beneficial vascular effects of α-tocopherol. Recent data have shown that apart from indirect protection of NO from inactivation, α-tocopherol exerts a direct stimulatory effect on eNOS activation via serine 1177 phosphorylation. This effect was amplified by ascorbic acid suggesting that both compounds may act synergistically in optimizing endothelial NO synthesis. The data obtained in cell culture and animal studies are promising, but human long-term studies are needed to determine whether the described mechanisms are active in vivo and may provide a rationale for optimizing dietary or supplementary intake of antioxidant vitamins in certain subsets of patients.

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Acknowledgements

Experimental work was supported by the Interdisziplinäres Zentrum für Klinische Forschung, Klinikum der Friedrich-Schiller-Universität Jena (to R.H.), the Austrian research funds “Zur Förderung der wissenschaftlichen Forschung,” project P16059 (to G.W.-F.) and project 16 188 (to E.R.W.). We thank Gunda Guhr, Elke Teuscher and Petra Loitzl for their excellent technical assistance.

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Authors and Affiliations

  1. Institute of Molecular Cell Biology, Friedrich-Schiller-University of Jena, Nonnenplan 2, 07743, Jena, Germany

    Regine Heller

  2. Biocentre, Division of Biological Chemistry, Innsbruck Medical University, 6020, Innsbruck, Austria

    Gabriele Werner-Felmayer & Ernst R. Werner

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  1. Regine Heller
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  2. Gabriele Werner-Felmayer
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Correspondence to Regine Heller.

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Heller, R., Werner-Felmayer, G. & Werner, E.R. Antioxidants and endothelial nitric oxide synthesis. Eur J Clin Pharmacol 62 (Suppl 1), 21–28 (2006). https://doi.org/10.1007/s00228-005-0009-7

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