EXPRESSION OF THE INDUCIBLE NITRIC-OXIDE SYNTHASE GENE IN DIAPHRAGM AND SKELETAL-MUSCLE

Nitric oxide (NO) is a pluripotent molecule that can be secreted by sk eletal muscle through the activity of the neuronal constitutive isofor m of NO synthase. To determine whether skeletal muscle and diaphragm m ight also express the macrophage-inducible form of NO synthase (iNOS) during provocative states, we examined tissue from mice at serial time s after intravenous administration of Escherichia coli endotoxin. In t hese studies, iNOS mRNA was strongly expressed in the diaphragm and sk eletal muscle of mice 4 h after intravenous endotoxin and was signific antly diminished by 8 h after challenge. Induction of iNOS mRNA was fo llowed by expression of iNOS immunoreactive protein on Western immunob lots. Increased iNOS activity was demonstrated by conversion of argini ne to citrulline. Immunochemical analysis of diaphragmatic explants ex posed to endotoxin in vitro revealed specific iNOS staining in myocyte s, in addition to macrophages and endothelium. These results may be im portant in understanding the pathogenesis of respiratory pump failure during septic shock, as well as skeletal muscle injury during inflamma tion or metabolic stress.