title: Reduction of experimental vein graft intimal hyperplasia and preservation of nitric oxide-mediated relaxation by the nitric oxide precursor L-arginine.
abstract: BACKGROUND
  Previous studies in animals and human beings have shown that vein bypass grafts exhibit diminished endothelium-dependent relaxation and the development of intimal hyperplasia. This study examines the effect of L-arginine on experimental vein graft endothelial cell function and the development of intimal hyperplasia.
  
  
  METHODS
  Common carotid vein bypass grafts were performed in 24 New Zealand White rabbits: 12 were controls and 12 received L-arginine (2.25%) orally 7 days before operation and thereafter until harvest 28 days after operation. Intimal and medial dimensions were determined by planimetry on pressure-fixed vessels. Relaxation to acetylcholine, serotonin, calcium ionophore (A23187), and sodium nitroprusside was performed on precontracted vessel rings.
  
  
  RESULTS
  Arginine-treated vein grafts showed a 47% reduction in mean intimal thickness (p < 0.001) compared with controls. By scanning and transmission electron microscopy, all vein grafts showed a confluent endothelium. In contrast to control grafts, which do not relax to acetylcholine and serotonin, arginine-treated vein grafts relaxed in response to both agonists. There was a significant increase (p < 0.05) in the maximal relaxation to calcium ionophore (A23187) in arginine-treated vein grafts compared with control grafts. Non-endothelium-dependent responses to sodium nitroprusside were equivalent in all vein grafts.
  
  
  CONCLUSIONS
  This study shows that oral L-arginine supplementation significantly reduces intimal hyperplasia and preserves nitric oxide-mediated relaxation in experimental vein grafts, suggesting a role for nitric oxide in the regulation of the cellular events that lead to intimal hyperplasia.
authors.affiliation: Department of Surgery, Duke University Medical Center, Durham, N.C. 27710.
authors.forename: M G
authors.initials: MG
authors.lastname: Davies
authors.forename: J H
authors.initials: JH
authors.lastname: Kim
authors.forename: H
authors.initials: H
authors.lastname: Dalen
authors.forename: R G
authors.initials: RG
authors.lastname: Makhoul
authors.forename: E
authors.initials: E
authors.lastname: Svendsen
authors.forename: P O
authors.initials: PO
authors.lastname: Hagen
mesh_terms: D000818:Animals; D001120:Arginine / Q000494:pharmacology / Q000627:therapeutic use*; D017536:Carotid Artery, Common / Q000601:surgery; D004305:Dose-Response Relationship, Drug; D006083:Graft Occlusion, Vascular / Q000503:physiopathology / Q000517:prevention & control*; D006965:Hyperplasia / Q000188:drug therapy; D007601:Jugular Veins / Q000187:drug effects / Q000502:physiology / Q000637:transplantation*; D009569:Nitric Oxide; D011817:Rabbits; D017539:Tunica Intima / Q000187:drug effects / Q000473:pathology* / Q000502:physiology; D014661:Vasoconstriction / Q000187:drug effects; D014664:Vasodilation / Q000187:drug effects
chemical_list: D009569:Nitric Oxide; D001120:Arginine