title: Activation of endothelial nitric oxide synthase by red wine polyphenols: impact of grape cultivars, growing area and the vinification process.
abstract: OBJECTIVE
  Accumulating data document protective effects of red wine in cardiovascular disease by improved nitric oxide bioavailability. Not all wines, however, seem to be equally effective. The aim of the present study was to elucidate the impact of grape cultivars, growing area and the vinification/fermentation process on the ability of red wine polyphenol extracts to increase human endothelial nitric oxide synthase (eNOS) promotor and enzyme activity.
  
  
  METHODS
  We produced polyphenol extracts from a variety of red wines from all over the world and tested their influence on eNOS promotor activity by a luciferase reporter gene assay. Selected extracts were subjected to the L-arginine-L-citrulline conversion assay to confirm that enhanced eNOS transcription results in enhanced enzyme activity.
  
  
  RESULTS
  We show that polyphenol extracts from wines of specific origin and grape cultivars vary strongly in their individual activity. However, when averaged, the activity could not be attributed to a specific grape cultivar or growing area. Resveratrol alone significantly enhanced eNOS promotor and enzyme activity, although at concentrations higher than those available in effective concentrations of red wine polyphenol extracts. Extracts of grape juice showed activity as well.
  
  
  CONCLUSIONS
  The biological activity of red wines on eNOS transcription depends neither on grape cultivars nor on growing area in general. Resveratrol may be the most promising ingredient in red wine polyphenol extracts, but does not account for the complete effect. A large part of the active components are genuine grape compounds, since extracts of grape juice that did not undergo a fermentation process also showed activity.
authors.affiliation: Department of Pharmacy, Center of Drug Research, University of Munich, Munich, Germany.
authors.forename: Thomas R
authors.initials: TR
authors.lastname: Räthel
authors.forename: Rainer
authors.initials: R
authors.lastname: Samtleben
authors.forename: Angelika M
authors.initials: AM
authors.lastname: Vollmar
authors.forename: Verena M
authors.initials: VM
authors.lastname: Dirsch
mesh_terms: D002460:Cell Line; D002980:Climate; D004305:Dose-Response Relationship, Drug; D042783:Endothelial Cells / Q000187:drug effects* / Q000378:metabolism; D005285:Fermentation; D005419:Flavonoids / Q000032:analysis / Q000494:pharmacology*; D017930:Genes, Reporter; D005843:Geography; D006801:Humans; D008156:Luciferases; D009569:Nitric Oxide / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000378:metabolism*; D010636:Phenols / Q000032:analysis / Q000494:pharmacology*; D059808:Polyphenols; D000077185:Resveratrol; D013267:Stilbenes / Q000032:analysis / Q000494:pharmacology*; D015854:Up-Regulation; D014665:Vasodilator Agents / Q000494:pharmacology*; D027843:Vitis / Q000737:chemistry* / Q000145:classification; D014920:Wine / Q000032:analysis / Q000145:classification
chemical_list: D005419:Flavonoids; D010636:Phenols; D059808:Polyphenols; D013267:Stilbenes; D014665:Vasodilator Agents; D009569:Nitric Oxide; D008156:Luciferases; D019001:Nitric Oxide Synthase; D000077185:Resveratrol