Induction of diaphragmatic nitric oxide synthase after endotoxin administration in rats: role on diaphragmatic contractile dysfunction

• Published in: The Journal of clinical investigation Vol. 98; no. 7; pp. 1550 - 1559
• Main Authors: Boczkowski, J, Lanone, S, Ungureanu-Longrois, D, Danialou, G, Fournier, T, Aubier, M
• Format: Journal Article
• Language: English
• Published: United States 01.10.1996
• Subjects: Abdominal Muscles - enzymology; Animals; Cyclic GMP - analysis; Dexamethasone - pharmacology; Diaphragm - drug effects; Diaphragm - enzymology; Diaphragm - physiopathology; Endotoxins - pharmacology; Enzyme Induction; Heart Ventricles - enzymology; Immunohistochemistry; Intercostal Muscles - enzymology; Male; Muscle Contraction - drug effects; Muscle, Skeletal - enzymology; Myocardium - enzymology; Nitric Oxide Synthase - biosynthesis; omega-N-Methylarginine - pharmacology; Rats; Rats, Sprague-Dawley; Stereoisomerism; Tissue Distribution
• ISSN: 0021-9738
• DOI: 10.1172/jci118948

Nitric oxide (NO), a free radical that is negatively inotropic in the heart and skeletal muscle, is produced in large amounts during sepsis by an NO synthase inducible (iNOS) by LPS and/or cytokines. The aim of this study was to examine iNOS induction in the rat diaphragm after Escherichia Coli LPS inoculation (1.6 mg/kg i.p.), and its involvement in diaphragmatic contractile dysfunction. Inducible NOS protein and activity could be detected in the diaphragm as early as 6 h after LPS inoculation. 6 and 12 h after LPS, iNOS was expressed in inflammatory cells infiltrating the perivascular spaces of the diaphragm, whereas 12 and 24 h after LPS it was expressed in skeletal muscle fibers. Inducible NOS was also expressed in the left ventricular myocardium, whereas no expression was observed in the abdominal, intercostal, and peripheral skeletal muscles. Diaphragmatic force was significantly decreased 12 and 24 h after LPS. This decrease was prevented by inhibition of iNOS induction by dexamethasone or by inhibition of iNOS activity by N(G)-methyl-L-arginine. We conclude that iNOS was induced in the diaphragm after E. Coli LPS inoculation in rats, being involved in the decreased muscular force.