Changes in gut mucosal nitric oxide synthase (NOS) activity after thermal injury and its relation with barrier failure

This study was designed to investigate changes in mucosal NOS activity afte r burns and its relation to barrier failure. In Experiment 1, female specif ic pathogen free (SPF) Sprague-Dawley rats underwent 35% total body surface area (TBSA) burn. One to six days after burn, intestinal permeability was determined from the plasma leakage of fluorescein isothiocyanate (FITC)-dex tran 4400, intestinal mucosal cNOS and iNOS activity were assayed using Gri ess' reagent, and the cellular localization of iNOS was examined using immu nostaining. In Experiment 2, S-methylisothiourea (SMT) was given (5 mg/kg, i.p. every 12 h) for 2 days to suppress inducible NOS (iNOS) activity after thermal injury. On postburn Day 2, the effect of SMT on gut mucosal NOS ac tivity, intestinal permeability, and barrier function were evaluated. The a ctivity of iNOS increased 24 h after the injury and up to a maximum of twof old on postburn Day 2, and decreased thereafter. The increase in iNOS activ ity in gut mucosa correlated well with the increase in intestinal permeabil ity, an index for barrier failure (r = .776, p = .0002). Results from iNOS immunostaining showed that changes in mucosal iNOS activity after the burn occurred mainly in the enterocytes rather than in the macrophages. Administ ration of SMT decreased mucosal iNOS activity, intestinal permeability, and bacterial translocation incidence to mesenteric lymph node concurrently. I n conclusion, thermal injury induces intestinal mucosal iNOS, which is prin cipally in the enterocytes. The increased intestinal iNOS activity was clos ely related to barrier failure. SMT inhibited intestinal mucosal iNOS activ ity and prevented barrier failure as demonstrated by a decrease in BT occur rence and intestinal permeability.