Endotoxin and TNF alpha directly stimulate nitric oxide formation in cultured rat hepatocytes from chronically endotoxemic rats

Biochem Biophys Res Commun. 1992 May 29;185(1):430-5. doi: 10.1016/s0006-291x(05)81003-4.


We examined the effects of endotoxin on nitric oxide formation in isolated rat hepatocytes in primary culture. Endotoxin was administered either in vivo, by continuous infusion for 30 or 3 h, or in vitro, on cultured cells. The spontaneous production of nitrites in hepatocytes from in vivo ET-infused rats was lower than equivalent saline controls in the absence of added stimuli. However in vitro addition of endotoxin in culture to hepatocytes from 30 h ET-infused rats greatly enhanced production relative to saline controls. This effect was mimicked by TNF alpha, and activators of protein kinase C (PMA and Ca2+ ionophore A23187). The effects of ET were blocked by NMMA, dexamethasone and protein synthesis inhibitors Actinomycin D and cycloheximide. No in vitro effect of ET was observed in the 3 h infusion model. The results show that chronic exposure to sub-lethal levels of ET primes liver parenchymal cells for the production of nitric oxide, when exposed in vitro to ET or TNF alpha.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Arginine / analogs & derivatives
  • Arginine / pharmacology
  • Cells, Cultured
  • Cycloheximide / pharmacology
  • Dactinomycin / pharmacology
  • Dexamethasone / pharmacology
  • Lipopolysaccharides / metabolism*
  • Liver / drug effects
  • Liver / metabolism*
  • Nitric Oxide / metabolism*
  • Rats
  • Toxemia / metabolism*
  • Tumor Necrosis Factor-alpha / pharmacology*
  • omega-N-Methylarginine


  • Lipopolysaccharides
  • Tumor Necrosis Factor-alpha
  • Dactinomycin
  • omega-N-Methylarginine
  • Nitric Oxide
  • Dexamethasone
  • Arginine
  • Cycloheximide