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

Abstract

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. ( J. Clin. Invest. 1996. 98:1550-1559.)

Regulation of nitric oxide production in limb and ventilatory muscles during chronic exercise training

“…However, the expression of this isoform is substantially induced in conditions where proinflammatory cytokines are elevated, such as sepsis in humans and endotoxemia in animals (7,15). Our study indicates that chronic exercise training does not elicit iNOS induction in limb and ventilatory muscles nor does it evoke upregulation of muscle AS and AL protein expression.…”

“…There is also evidence that excessive NO production primarily by the iNOS isoform may have deleterious effects on muscle contractile performance (7) and sarcolemmal integrity (16).…”

“…One possible mechanism through which chronic exercise training may elicit iNOS induction inside muscle fibers is the production of proinflammatory cytokines both systemically and within the working muscles. Exposure of muscles to proinflammatory cytokines induces muscle iNOS expression under both in vitro and in vivo conditions (7,29). Induction of iNOS is usually accompanied by increased requirements for L-arginine, which is supplied through active transport from the extracellular space, protein degradation, and recycling of L-citrulline to L-arginine.…”

Diesel particles increase phosphatidylcholine release through a NO pathway in alveolar type II cells

“…After an additional 24-h incubation period with DEPs or endotoxin from E. coli [lipopolysaccharide (LPS)], cells were scraped in buffer containing 50 mM Tris ⅐ HCl, pH 7.4, 0.1 mM EDTA, 1 M leupeptin, 1 M phenylmethylsulfonyl fluoride, and 1 M aprotinin and stored at Ϫ80°C until use. Western blot analysis was performed as previously described (7). Briefly, 50 g of total protein determined using a bicinchoninic acid protein assay were separated in SDS-7.5% polyacrylamide gels and transferred onto nitrocellulose membranes.…”

Lipopolysaccharide-Induced Increase of Prostaglandin E2 Is Mediated by Inducible Nitric Oxide Synthase Activation of the Constitutive Cyclooxygenase and Induction of Membrane-Associated Prostaglandin E Synthase

“…A low dose LPS-mediated activation of the NOS2 pathway (18,19) was obtained by i.p. injection of LPS (6 mg/kg body weight (bw)) to all rats, except those of the control group (n ϭ 4) that received 500 l of 0.9% NaCl i.p.…”