title: Endothelial nitric oxide synthase activity is essential for vasodilation during blood flow recovery but not for arteriogenesis.
abstract: OBJECTIVE
  Arteriogenesis is the major mechanism of vascular growth, which is able to compensate for blood flow deficiency after arterial occlusion. Endothelial nitric oxide synthase (eNOS) activity is essential for neovascularization, however its specific role in arteriogenesis remains unclear. We studied the role of eNOS in arteriogenesis using 3 mouse strains with different eNOS expression.
  
  
  RESULTS
  Distal femoral artery ligation was performed in eNOS-overexpressing mice (eNOStg), eNOS-deficient (eNOS-/-) mice, and wild type (WT) controls. Tissue perfusion and collateral-dependent blood flow were significantly increased in eNOStg mice compared with WT only immediately after ligation. In eNOS-/- mice, although tissue perfusion remained significantly decreased, collateral-dependent blood flow was only decreased until day 7, suggesting normal, perhaps delayed collateral growth. Histology confirmed no differences in collateral arteries of eNOStg, eNOS-/-, and WT mice at 1 and 3 weeks. Administration of an NO donor induced vasodilation in collateral arteries of eNOS-/- mice, but not in WT, identifying the inability to vasodilate collateral arteries as main cause of impaired blood flow recovery in eNOS-/- mice.
  
  
  CONCLUSIONS
  This study demonstrates that eNOS activity is crucial for NO-mediated vasodilation of peripheral collateral vessels after arterial occlusion but not for collateral artery growth.
authors.affiliation: Department of Cell Biology & Genetics, Erasmus University MC Rotterdam, Dr. Molewaterplein 50, 3015 GE Rotterdam, The Netherlands. b.mees@erasmusmc.nl
authors.forename: Barend
authors.initials: B
authors.lastname: Mees
authors.forename: Shawn
authors.initials: S
authors.lastname: Wagner
authors.forename: Elena
authors.initials: E
authors.lastname: Ninci
authors.forename: Silvia
authors.initials: S
authors.lastname: Tribulova
authors.forename: Sandra
authors.initials: S
authors.lastname: Martin
authors.forename: Rien
authors.initials: R
authors.lastname: van Haperen
authors.forename: Sawa
authors.initials: S
authors.lastname: Kostin
authors.forename: Matthias
authors.initials: M
authors.lastname: Heil
authors.forename: Rini
authors.initials: R
authors.lastname: de Crom
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Schaper
mesh_terms: D000818:Animals; D003097:Collateral Circulation / Q000502:physiology; D004195:Disease Models, Animal; D005263:Femoral Artery / Q000293:injuries; D051379:Mice; D008822:Mice, Transgenic; D018919:Neovascularization, Physiologic / Q000502:physiology*; D009569:Nitric Oxide / Q000378:metabolism*; D052247:Nitric Oxide Synthase Type II / Q000235:genetics / Q000378:metabolism*; D052250:Nitric Oxide Synthase Type III; D014664:Vasodilation / Q000502:physiology*
chemical_list: D009569:Nitric Oxide; D052247:Nitric Oxide Synthase Type II; D052250:Nitric Oxide Synthase Type III; C496315:Nos3 protein, mouse