Nitric oxide synthase isoforms play distinct roles during acute peritonitis

Area of Science:

• Nephrology
• Physiology
• Molecular Biology

Background:

• Acute peritonitis is a common complication of peritoneal dialysis (PD).
• Increased nitric oxide (NO) production by NO synthase (NOS) isoforms is linked to peritonitis, but their specific roles in the peritoneum are unclear.

Purpose of the Study:

• To investigate the roles of endothelial NOS (eNOS), inducible NOS (iNOS), and neuronal NOS (nNOS) in acute peritonitis during PD.
• To determine the functional consequences of NOS isoform deficiency on peritoneal membrane transport and NO metabolite levels.

Main Methods:

• Acute peritonitis was induced by lipopolysaccharide (LPS) in wild-type (WT) and NOS isoform knockout (KO) mice (eNOS, iNOS, nNOS).
• Peritoneal membrane transport, ultrafiltration, dialysate NO metabolites (NOx), and inflammatory markers were assessed.

Main Results:

• LPS increased small solute transport and decreased ultrafiltration in WT mice, associated with NOS upregulation.
• Transport modifications were reversed in eNOS KO mice, but not in iNOS or nNOS KO mice.
• Dialysate NOx increase was abolished in iNOS KO and reduced in eNOS KO mice, while iNOS deficiency worsened inflammation and mortality.

Conclusions:

• Specific NOS isoforms have distinct roles in the peritoneal membrane during acute peritonitis.
• Selective inhibition of eNOS may offer a therapeutic strategy to improve peritoneal transport in PD-associated peritonitis.