Inhibition of nitric oxide synthase reverses permeability changes in a mouse model of acute peritonitis.
Acute peritonitis is the most frequent complication of peritoneal dialysis. Previous studies have suggested a major role for nitric oxide (NO) in the permeability changes and loss of ultrafiltration induced by acute peritonitis. In this study, we further investigated the potential role of NO in a mouse model of peritonitis induced by Escherichia coli Lipopolysaccharide (LPS). A 2-hour peritoneal equilibration test was performed in control and LPS-treated mice using 7% glucose dialysate supplemented or not with the NO synthase inhibitor NG-nitro-L-arginine methyl ester (L-NAME). The levels of NO metabolites in the dialysate were maximal 18 hours after LPS injection. At that time, acute peritonitis induced by LPS was reflected by an increased recruitment of leukocytes, an increased intraperitoneal release of interleukin-6, a significant increase in the peritoneal permeability for small solutes, a loss of sodium sieving, and a loss of ultrafiltration in comparison with controls. Addition of L-NAME in LPS-treated mice significantly reversed permeability modifications and prevented the release of NO metabolites into the dialysate. These results confirm that increased NO mediates permeability modifications during acute peritonitis, and illustrate the potential of mouse models to investigate the molecular mechanisms regulating peritoneal permeability.
Ni
Jie
J
Division of Nephrology, Université Catholique de Louvain Medical School, Brussels, Belgium.
Cnops
Yvette
Y
McLoughlin
Rachel M
RM
Topley
Nicholas
N
Devuyst
Olivier
O
D000208:Acute Disease; D000818:Animals; D004791:Enzyme Inhibitors / Q000008:administration & dosage; D004926:Escherichia coli; D007263:Infusions, Parenteral; D008070:Lipopolysaccharides / Q000009:adverse effects*; D008297:Male; D051379:Mice; D023421:Models, Animal; D019331:NG-Nitroarginine Methyl Ester / Q000008:administration & dosage; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors* / Q000276:immunology; D010537:Peritoneum / Q000187:drug effects / Q000378:metabolism*; D010538:Peritonitis / Q000209:etiology / Q000503:physiopathology / Q000517:prevention & control*; D010539:Permeability
D004791:Enzyme Inhibitors; D008070:Lipopolysaccharides; D019001:Nitric Oxide Synthase; D019331:NG-Nitroarginine Methyl Ester