Interactions between inducible isoforms of nitric oxide synthase and cyclo-oxygenase in vivo: investigations using the selective inhibitors, 1400W and celecoxib

摘要

Exposure of tissues to endotoxin (LPS) and/or cytokines leads to the induction of both inducible nitric oxide synthase(iNOS) and cyclo-oxygenase-2(COX-2). It has previously been reported that three is 'cross-talk' between these two systems. However such previous studies have been limited by the availability of highly selective inhibitors. Here we have investigated the interactions between iNOS and COX-2 in vivo using 1400W, an iNOS-selective inhibitor, and celecoxib, a COX-2 selective inhibitor. Infusion of LPS to rats for 6 h caused a time-dependent increase in the plasma concentrations of 6 Keto-prostaglandin F_1α(6 keto-PGF_1α) and nitriteitrate(NO_2/NO_3), consistent with the induction of INOS and COX-2.