Expression of the inducible nitric oxide synthase (inos) gene in
diaphragm and skeletal muscle.
Thompson, Marita, Lisa Becker, Debbie Bryant, Gary Williams, Daniel
Levin, Linda Margraf, and Brett P. Giroir.
The Laboratories for Molecular Biology and Physiology Research,
Department of Pediatrics, and The Department of Pathology, The
University of Texas Southwestern Medical Center, Dallas, Texas,
75235-9063
APStracts 3:0398A, 1996.
Nitric oxide (NO) is a pluripotent molecule which can be secreted by
skeletal muscle through the activity of the neuronal constitutive
isoform of nitric oxide synthase (nc-NOS). To determine whether
skeletal muscle and diaphragm might also express the macrophage
inducible form of nitric oxide synthase (iNOS) during provocative
states, we examined tissue from mice at serial times following
intravenous administration of E. coli endotoxin. In these studies,
iNOS mRNA was strongly expressed in the diaphragm and skeletal muscle
of mice 4 hours after intravenous endotoxin, and was significantly
diminished by 8 hours following 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.
Received 16 March 1995; accepted in final form 26 July 1996.
APS Manuscript Number A286-5.
Article publication pending Journal of Applied Physiology.
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 29 August 1996