Inhibition of nitric oxide synthase reverses changes in peritoneal permeability in a rat model of acute peritonitis

Background. Acute peritonitis is the most frequent complication of peritone al dialysis (PD), and nitric oxide (NO) is thought to play a role in the st ructural and permeability changes observed in this condition. We have used a combination of expression, enzymatic and pharmacological studies to subst antiate the potential role(s) played by NO during peritonitis. Methods. The peritoneal equilibration test was performed in control rats an d rats with acute peritonitis (originating from skin flora), using standard dialysate supplemented or not with the NO synthase (NOS) inhibitor N-G-nit ro-L-arginine methyl ester (L-NAME). In parallel, peritoneal NOS enzymatic activities were measured and expression studies for NOS isoforms and S-nitr osocysteine reactivity performed in the peritoneum. Results. In comparison with controls, rats with acute peritonitis were char acterized by inflammatory changes, increased S-nitrosocysteine immunoreacti vity, and increased NOS activities in the peritoneum, due td the up-regulat ion of endothelial and inducible NOS. In parallel, rats with acute peritoni tis showed increased permeability for small solutes; decreased sodium sievi ng; loss of ultrafiltration (UF); and increased protein loss in the dialysa te. Addition of L-NAME to the dialysate did not induce permeability changes in control rats, but significantly improved UF and reversed permeability m odifications in rats with peritonitis. The effect of L-NAME was reflected b y 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 regulatio n of peritoneal permeability during acute peritonitis in rats. By itself, N OS inhibition improves UF and reverses permeability changes, which might of fer new therapeutic perspectives in acute peritonitis.