title: Nitric oxide synthase isoforms play distinct roles during acute peritonitis.
abstract: BACKGROUND
  Acute peritonitis is the most frequent complication of peritoneal dialysis (PD). Increased nitric oxide (NO) release by NO synthase (NOS) isoforms has been implicated in acute peritonitis, but the role played by the NOS isoforms expressed in the peritoneum is unknown.
  
  
  METHODS
  We investigated the structural and functional consequences of acute peritonitis induced by LPS in wild-type (WT) mice versus knockout mice (KO) for the endothelial NOS (eNOS), the inducible NOS (iNOS) or the neuronal NOS (nNOS).
  
  
  RESULTS
  The level of NO metabolites (NOx) in the dialysate was maximal 18 h after LPS injection. LPS induced a significant increase in the transport of small solutes and decreased ultrafiltration in WT mice. These changes, which occurred without vascular proliferation, were paralleled by the upregulation of nNOS and eNOS, and the induction of iNOS. The transport modifications induced by LPS were significantly reversed in eNOS KO mice, but not modified in mice lacking iNOS or nNOS. In contrast, the increase of dialysate NOx was abolished in iNOS KO mice and significantly reduced in eNOS KO mice, but left unchanged in mice lacking nNOS. Mice lacking iNOS also showed more severe inflammatory changes, and a trend towards increased mortality following LPS.
  
  
  CONCLUSIONS
  These data demonstrate specific roles for NOS isoforms in the peritoneal membrane and suggest that selective eNOS inhibition may improve peritoneal transport during acute peritonitis.
authors.affiliation: Université catholique de Louvain Medical School, Brussels, Belgium.
authors.forename: Jie
authors.initials: J
authors.lastname: Ni
authors.forename: Rachel M
authors.initials: RM
authors.lastname: McLoughlin
authors.forename: Alexandre
authors.initials: A
authors.lastname: Brodovitch
authors.forename: Pierre
authors.initials: P
authors.lastname: Moulin
authors.forename: Peter
authors.initials: P
authors.lastname: Brouckaert
authors.forename: Barbara
authors.initials: B
authors.lastname: Casadei
authors.forename: Olivier
authors.initials: O
authors.lastname: Feron
authors.forename: Nicholas
authors.initials: N
authors.lastname: Topley
authors.forename: Jean-Luc
authors.initials: JL
authors.lastname: Balligand
authors.forename: Olivier
authors.initials: O
authors.lastname: Devuyst
mesh_terms: D000208:Acute Disease; D000818:Animals; D004195:Disease Models, Animal; D007527:Isoenzymes / Q000502:physiology; D008070:Lipopolysaccharides / Q000009:adverse effects; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D052248:Nitric Oxide Synthase Type I / Q000235:genetics / Q000502:physiology*; D052247:Nitric Oxide Synthase Type II / Q000235:genetics / Q000502:physiology*; D052250:Nitric Oxide Synthase Type III / Q000235:genetics / Q000502:physiology*; D010537:Peritoneum / Q000201:enzymology / Q000473:pathology; D010538:Peritonitis / Q000139:chemically induced / Q000201:enzymology* / Q000503:physiopathology*
chemical_list: D007527:Isoenzymes; D008070:Lipopolysaccharides; D052248:Nitric Oxide Synthase Type I; D052247:Nitric Oxide Synthase Type II; D052250:Nitric Oxide Synthase Type III
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