title: Pharmacologic relaxation of vein grafts is beneficial compared with pressure distention caused by upregulation of endothelial nitric oxide synthase and nitric oxide production.
abstract: OBJECTIVE
  Pressure distention of veins during preparation for bypass surgery is believed to impair vascular integrity and reduce graft patency. We previously suggested a combination of pharmacologic vasodilatators as an alternative to distention. Vascular homeostasis is largely regulated by nitric oxide. We investigated the role of distention in comparison with pharmacologic vasorelaxation in the regulation of nitric oxide synthases, nitric oxide bioavailability, and vascular reactivity in vein grafts.
  
  
  METHODS
  In a porcine model the internal jugular vein from either side received pressure distention or the combination of vasodilators (alpha-adrenergic antagonist, phenoxybenzamine, 10 micromol/L; Rho-kinase inhibitor, HA-1077 [fasudil], 50 mumol/L; calcium blocker, nicardipine, 1 micromol/L) and then was grafted into the carotid artery. Regulation of nitric oxide synthase, as well as nitrate and nitrite levels, were examined in vein grafts after 2 weeks of implantation.
  
  
  RESULTS
  Distention of jugular veins resulted in reduction of vasoconstriction in response to depolarization and agonist stimulation. Arterial grafting doubled inducible nitric oxide synthase expression in both grafts but caused a pronounced upregulation of endothelial nitric oxide synthase protein (by 57.3% +/- 5%) only in drug-treated grafts, whereas in distended grafts the endothelial nitric oxide synthase level was decreased by 27.5% +/- 2.7%. The downregulated endothelial nitric oxide synthase level in the distended grafts was accompanied by a 45.2% +/- 3.1% reduction of phospho-endothelial nitric oxide synthase Ser1177 levels and by a significant reduction in nitric oxide synthase activity (12.1% +/- 1.2%) and nitrate production (48.9% +/- 5.6%) in comparison with that seen in drug-treated grafts.
  
  
  CONCLUSIONS
  Pharmacologic preparation of the vein grafts results in upregulation of endothelial nitric oxide synthase and increased nitric oxide production in the vein grafts after arterial implantation. This might provide greater clinical benefit than conventional pressure-distention methods.
authors.affiliation: James Hogg iCAPTURE Center for the Cardiovascular and Pulmonary Research, St Paul's Hospital, Vancouver, British Columbia, Canada. achung@mrl.ubc.ca
authors.forename: Ada W Y
authors.initials: AW
authors.lastname: Chung
authors.forename: Pooja
authors.initials: P
authors.lastname: Rauniyar
authors.forename: Honglin
authors.initials: H
authors.lastname: Luo
authors.forename: York N
authors.initials: YN
authors.lastname: Hsiang
authors.forename: Cornelis
authors.initials: C
authors.lastname: van Breemen
authors.forename: Elena B
authors.initials: EB
authors.lastname: Okon
mesh_terms: D000818:Animals; D004548:Elasticity; D005260:Female; D009569:Nitric Oxide / Q000096:biosynthesis*; D019001:Nitric Oxide Synthase / Q000096:biosynthesis; D052250:Nitric Oxide Synthase Type III / Q000096:biosynthesis*; D011312:Pressure; D013552:Swine; D015854:Up-Regulation / Q000187:drug effects*; D014664:Vasodilation / Q000187:drug effects; D014665:Vasodilator Agents / Q000494:pharmacology*; D014680:Veins / Q000187:drug effects* / Q000502:physiology / Q000637:transplantation*
chemical_list: D014665:Vasodilator Agents; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D052250:Nitric Oxide Synthase Type III