title: Tetrahydrobiopterin improves endothelial function in human saphenous veins.
abstract: OBJECTIVE
  Diminished production of nitric oxide has been linked to saphenous vein endothelial dysfunction. Tetrahydrobiopterin is an obligate cofactor for the oxidation of L -arginine by nitric oxide synthase in the production of nitric oxide by endothelial cells. The objective of the present study was to examine whether the exogenous addition of tetrahydrobiopterin improves endothelial function in saphenous veins from patients undergoing coronary artery bypass graft operations.
  
  
  METHODS
  Vascular segments of saphenous veins were obtained from 17 patients undergoing elective coronary artery bypass grafting, and in vitro endothelium-dependent and endothelium-independent responses to acetylcholine and sodium nitroprusside were assessed. Isometric dose-response curves were constructed in precontracted rings in the presence and absence of tetrahydrobiopterin (0.1 mmol/L) with the use of the organ bath apparatus. The percentages of maximum relaxation and sensitivity were compared between interventions.
  
  
  RESULTS
  Acetylcholine caused dose-dependent endothelium-mediated relaxation in saphenous veins. In the presence of tetrahydrobiopterin, acetylcholine-induced relaxation was significantly augmented (percentage maximum relaxation, 16.8% +/- 2.9% vs control 7.5% +/- 1.8%; P =.003) without an effect on agonist sensitivity. These effects were endothelium-specific because endothelium-independent responses to sodium nitroprusside were preserved.
  
  
  CONCLUSIONS
  These data uncover beneficial effects of acute tetrahydrobiopterin addition on endothelial function in human vessels. Because endothelial dysfunction has been implicated in the development of graft failure, studies aimed at chronic delivery of tetrahydrobiopterin would be useful in determining the contribution of this cofactor toward saphenous vein atherosclerosis.
authors.affiliation: Divisions of Cardiology, Pharmacology, and Cardiac Surgery, Faculty of Medicine, The University of Calgary, Calgary, Alberta, Canada.
authors.forename: S
authors.initials: S
authors.lastname: Verma
authors.forename: F
authors.initials: F
authors.lastname: Lovren
authors.forename: A S
authors.initials: AS
authors.lastname: Dumont
authors.forename: K J
authors.initials: KJ
authors.lastname: Mather
authors.forename: A
authors.initials: A
authors.lastname: Maitland
authors.forename: T M
authors.initials: TM
authors.lastname: Kieser
authors.forename: C R
authors.initials: CR
authors.lastname: Triggle
authors.forename: T J
authors.initials: TJ
authors.lastname: Anderson
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology; D000704:Analysis of Variance; D000975:Antioxidants / Q000494:pharmacology*; D001708:Biopterins / Q000031:analogs & derivatives* / Q000494:pharmacology; D001026:Coronary Artery Bypass; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000187:drug effects*; D006801:Humans; D066298:In Vitro Techniques; D009599:Nitroprusside / Q000494:pharmacology; D012501:Saphenous Vein / Q000187:drug effects*; D014664:Vasodilation / Q000187:drug effects; D014665:Vasodilator Agents / Q000494:pharmacology
chemical_list: D000975:Antioxidants; D014665:Vasodilator Agents; D009599:Nitroprusside; D001708:Biopterins; C003402:sapropterin; D000109:Acetylcholine