title: Daily red wine consumption improves vascular function by a soluble guanylyl cyclase-dependent pathway.
abstract: BACKGROUND
  Polyphenols in red wine are supposed to improve endothelial function. We investigated whether daily red wine consumption improves in-vivo vascular function by reducing endothelin-1 (ET-1). Additional pathways mediating this effect were studied using porcine coronary arteries (PCAs).
  
  
  METHODS
  Eighteen young healthy women drank red wine daily for 3 weeks. Vascular function was evaluated by determining forearm blood flow (FBF) responses to endothelium-dependent (acetylcholine (ACh)) and endothelium-independent (sodium nitroprusside (SNP)) vasodilators. PCAs were suspended in organ baths and exposed to the endothelium-dependent vasodilator bradykinin, the nitric oxide (NO) donor S-nitroso-N-acetyl-L,L-penicillamine (SNAP) and/or red wine extract (RWE).
  
  
  RESULTS
  ACh-induced and SNP-induced FBF increases were equally enhanced after 3 weeks of red wine consumption, but an immediate enhancement (i.e., after drinking the first glass) was not observed. Vice versa, plasma ET-1 levels were not decreased after 3 weeks, but we observed an acute drop after drinking one glass of wine. RWE relaxed preconstricted PCAs in an endothelium-, NO-, and soluble guanylyl cyclase (sGC)/guanosine-3',5'-cyclic monophosphate (cGMP)-dependent manner. Short RWE exposure reduced the response to bradykinin and SNAP by inactivating sGC. This effect disappeared upon prolonged RWE exposure.
  
  
  CONCLUSIONS
  The enhanced FBF response following 3 weeks of red wine consumption, but not after one glass, reflects a change in smooth muscle sensitivity. Alterations in sGC responsiveness/activity, rather than changes in ET-1, appear to underlie this phenomenon.
authors.affiliation: Department of Internal Medicine, Erasmus University Medical Center, Rotterdam, The Netherlands.
authors.forename: Ilse P G
authors.initials: IP
authors.lastname: Botden
authors.forename: Janneke G
authors.initials: JG
authors.lastname: Langendonk
authors.forename: Marcel E
authors.initials: ME
authors.lastname: Meima
authors.forename: Frans
authors.initials: F
authors.lastname: Boomsma
authors.forename: Ann L B
authors.initials: AL
authors.lastname: Seynhaeve
authors.forename: Timo L M
authors.initials: TL
authors.lastname: ten Hagen
authors.forename: A H
authors.initials: AH
authors.lastname: Jan Danser
authors.forename: Eric J G
authors.initials: EJ
authors.lastname: Sijbrands
mesh_terms: D000328:Adult; D000428:Alcohol Drinking; D000818:Animals; D015415:Biomarkers / Q000097:blood; D002478:Cells, Cultured; D003331:Coronary Vessels / Q000187:drug effects / Q000201:enzymology; D004305:Dose-Response Relationship, Drug; D042783:Endothelial Cells / Q000187:drug effects / Q000201:enzymology; D019332:Endothelin-1 / Q000097:blood; D005260:Female; D005542:Forearm / Q000098:blood supply*; D006162:Guanylate Cyclase / Q000378:metabolism*; D006801:Humans; D066298:In Vitro Techniques; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000201:enzymology; D009569:Nitric Oxide / Q000378:metabolism; D010477:Perfusion; D010991:Plethysmography; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism*; D012039:Regional Blood Flow / Q000187:drug effects; D015398:Signal Transduction / Q000187:drug effects; D000071756:Soluble Guanylyl Cyclase; D013552:Swine; D013997:Time Factors; D014664:Vasodilation / Q000187:drug effects*; D014665:Vasodilator Agents / Q000494:pharmacology*; D014920:Wine; D055815:Young Adult
chemical_list: D015415:Biomarkers; D019332:Endothelin-1; D018160:Receptors, Cytoplasmic and Nuclear; D014665:Vasodilator Agents; D009569:Nitric Oxide; D006162:Guanylate Cyclase; D000071756:Soluble Guanylyl Cyclase