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Laboratories for Molecular Biology and Physiology Research, Department of Pediatrics, and Department of Pathology, The University of Texas Southwestern Medical Center, Dallas, Texas 75235-9063
Received 16 March 1995; accepted in final form 26 July 1996.
Thompson, Marita, Lisa Becker, Debbie Bryant, Gary Williams,
Daniel Levin, Linda Margraf, and Brett P. Giroir. Expression of
the inducible nitric oxide synthase gene in diaphragm and skeletal muscle. J. Appl. Physiol. 81(6):
2415-2420, 1996.
Nitric oxide (NO) is a pluripotent molecule that
can be secreted by skeletal muscle through the activity of the neuronal
constitutive isoform of NO synthase. To determine whether skeletal
muscle and diaphragm might also express the macrophage-inducible form
of NO synthase (iNOS) during provocative states, we examined tissue
from mice at serial times after intravenous administration of
Escherichia coli endotoxin. In these
studies, iNOS mRNA was strongly expressed in the diaphragm and skeletal
muscle of mice 4 h after intravenous endotoxin and was significantly
diminished by 8 h after challenge. Induction of iNOS mRNA was followed
by expression of iNOS immunoreactive protein on Western immunoblots.
Increased iNOS activity was demonstrated by conversion of arginine to
citrulline. Immunochemical analysis of diaphragmatic explants exposed
to endotoxin in vitro revealed specific iNOS staining in myocytes, in
addition to macrophages and endothelium. These results may be important
in understanding the pathogenesis of respiratory pump failure during
septic shock, as well as skeletal muscle injury during inflammation or
metabolic stress.
endotoxin; cytokines; septic shock
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