title: Inhibition of nitric oxide synthase reverses changes in peritoneal permeability in a rat model of acute peritonitis.
abstract: BACKGROUND
  Acute peritonitis is the most frequent complication of peritoneal dialysis (PD), and nitric oxide (NO) is thought to play a role in the structural and permeability changes observed in this condition. We have used a combination of expression, enzymatic and pharmacological studies to substantiate the potential role(s) played by NO during peritonitis.
  
  
  METHODS
  The peritoneal equilibration test was performed in control rats and rats with acute peritonitis (originating from skin flora), using standard dialysate supplemented or not with the NO synthase (NOS) inhibitor N(G)-nitro-L-arginine methyl ester (L-NAME). In parallel, peritoneal NOS enzymatic activities were measured and expression studies for NOS isoforms and S-nitrosocysteine reactivity performed in the peritoneum.
  
  
  RESULTS
  In comparison with controls, rats with acute peritonitis were characterized by inflammatory changes, increased S-nitrosocysteine immunoreactivity, and increased NOS activities in the peritoneum, due to the up-regulation of endothelial and inducible NOS. In parallel, rats with acute peritonitis showed increased permeability for small solutes; decreased sodium sieving; loss of ultrafiltration (UF); and increased protein loss in the dialysate. Addition of L-NAME to the dialysate did not induce permeability changes in control rats, but significantly improved UF and reversed permeability modifications in rats with peritonitis. The effect of L-NAME was reflected by a mild but consistent increase in blood pressure during PD exchange.
  
  
  CONCLUSIONS
  Our results demonstrate that local generation of NO, secondary to up-regulation of NOS isoforms, plays an important role in the regulation of peritoneal permeability during acute peritonitis in rats. By itself, NOS inhibition improves UF and reverses permeability changes, which might offer new therapeutic perspectives in acute peritonitis.
authors.affiliation: Division of Nephrology, Université Catholique de Louvain Medical School, Brussels, Belgium.
authors.forename: M L
authors.initials: ML
authors.lastname: Ferrier
authors.forename: S
authors.initials: S
authors.lastname: Combet
authors.forename: M
authors.initials: M
authors.lastname: van Landschoot
authors.forename: M S
authors.initials: MS
authors.lastname: Stoenoiu
authors.forename: Y
authors.initials: Y
authors.lastname: Cnops
authors.forename: N
authors.initials: N
authors.lastname: Lameire
authors.forename: O
authors.initials: O
authors.lastname: Devuyst
mesh_terms: D000208:Acute Disease; D000818:Animals; D003545:Cysteine / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II; D052250:Nitric Oxide Synthase Type III; D010537:Peritoneum / Q000378:metabolism* / Q000473:pathology; D010538:Peritonitis / Q000378:metabolism* / Q000473:pathology; D010539:Permeability; D051381:Rats; D017207:Rats, Sprague-Dawley; D026403:S-Nitrosothiols / Q000493:pharmacokinetics
chemical_list: D004791:Enzyme Inhibitors; D026403:S-Nitrosothiols; C021315:S-nitrosocysteine; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; D052250:Nitric Oxide Synthase Type III; C496318:Nos2 protein, rat; C496316:Nos3 protein, rat; D003545:Cysteine; D019331:NG-Nitroarginine Methyl Ester