title: Endothelial nitric oxide synthase is not essential for the development of fibrosis and portal hypertension in bile duct ligated mice.
abstract: OBJECTIVE
  It is postulated that nitric oxide (NO) is responsible for the hyperdynamic circulation of portal hypertension. Therefore, we investigated induction of fibrosis and hyperdynamic circulation in endothelial NO synthase knock-out (KO) mice.
  
  
  METHODS
  Fibrosis was induced by bile duct ligation. Hemodynamic studies were performed after portal vein ligation. All studies were performed in wild-type (WT) and KO mice.
  
  
  RESULTS
  Three to 4 weeks after bile duct ligation (BDL), both WT and KO groups had similar degrees of portal hypertension, 12 (9-14) and 11(8-15) mmHg, median (range), and liver function. Fibrosis increased from 0.0% in sham operated to 1.0 and 1.1% in WT and KO mice, respectively. Cardiac output was similar after portal vein ligation (20 and 17 ml/min in WT and KO mice, respectively). There was no difference in liver of mRNA for endothelin 1, inducible NO synthase (iNOS) and hem-oxygenase 1 (HO1); proteins of iNOS, HO1 and HO2; nor in endothelin A and B (EtA and EtB) receptor density between WT and KO mice after BDL.
  
  
  CONCLUSIONS
  These results suggest that endothelial NO synthase is neither essential for the development of fibrosis and portal hypertension in bile duct ligated mice, nor for the hyperdynamic circulation associated with portal hypertension in the portal vein ligated mice.
authors.affiliation: Institute for Clinical Pharmacology, University of Bern, Murtenstrasse 35, 3010 Bern, Switzerland.
authors.forename: Abraham
authors.initials: A
authors.lastname: Koshy
authors.forename: Andrea
authors.initials: A
authors.lastname: De Gottardi
authors.forename: Monika
authors.initials: M
authors.lastname: Ledermann
authors.forename: Hans
authors.initials: H
authors.lastname: Saegesser
authors.forename: Sidney G
authors.initials: SG
authors.lastname: Shaw
authors.forename: Arthur
authors.initials: A
authors.lastname: Zimmermann
authors.forename: Jürg
authors.initials: J
authors.lastname: Reichen
mesh_terms: D000818:Animals; D001652:Bile Ducts; D004195:Disease Models, Animal; D019332:Endothelin-1 / Q000235:genetics; D006419:Heme Oxygenase (Decyclizing) / Q000235:genetics; D051547:Heme Oxygenase-1 / Q000235:genetics; D006975:Hypertension, Portal / Q000209:etiology* / Q000503:physiopathology; D008026:Ligation; D008099:Liver / Q000503:physiopathology; D008103:Liver Cirrhosis / Q000209:etiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D052250:Nitric Oxide Synthase Type III / Q000235:genetics / Q000502:physiology*; D012333:RNA, Messenger / Q000032:analysis
chemical_list: D019332:Endothelin-1; D012333:RNA, Messenger; D052250:Nitric Oxide Synthase Type III; D006419:Heme Oxygenase (Decyclizing); D051547:Heme Oxygenase-1; C105245:heme oxygenase-2