Nitric oxide synthesis serves to reduce hepatic damage during acute murine endotoxemia

B. G. Harbrecht*, T. R. Billiar, J. Stadler, A. J. Demetris, J. B. Ochoa, R. D. Curran, R. L. Simmons

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

167 Scopus citations


Background and Methods: Nitric oxide synthesis occurs both in vitro and in vivo in response to inflammatory stimuli and can have profound effects on the local cellular environment. Hepatocytes, Kupffer cells, and endothelial cells produce nitric oxide in vitro, but the in vivo role of this reactive mediator in the liver is unknown. We assessed the role of nitric oxide synthesis during endotoxemia in mice by inhibiting its synthesis with N(G)-monomethyl- L-arginine after lipopolysaccharide injection and by determining the effects of this inhibition on hepatic damage. Results: Injection of lipopolysaccharide in mice increased plasma nitrite and nitrate concentrations, the stable end products of nitric oxide metabolism, and caused mild hepatic damage as measured by increased circulating hepatocellular enzyme levels. N(G)-monomethyl-L-arginine decreased plasma nitrite and nitrate values, but increased the lipopolysaccharide-induced hepatic injury. N(G)-monomethyl-L-arginine caused no hepatic damage when given without lipopolysaccharide. The extent of hepatic damage with N(G)- monomethyl-L-arginine was proportional to the dose of lipopolysaccharide used and could be reduced with concurrent administration of L-arginine but not D- arginine. Conclusions: Nitric oxide synthesis provides a protective function against lipopolysaccharide-induced liver injury that increases in importance as the degree of endotoxemia increases. The production of nitric oxide is, therefore, an important part of the liver's response to a systemic inflammatory stimulus.

Original languageEnglish
Pages (from-to)1568-1574
Number of pages7
JournalCritical Care Medicine
Issue number11
StatePublished - 1992
Externally publishedYes


  • arginine
  • circulatory shock
  • crit ical illness
  • cytokines
  • endotoxemia
  • endotoxin
  • hepatic failure
  • lipopolysaccharide
  • liver injury
  • nitrate
  • nitric oxide
  • nitrite
  • sepsis


Dive into the research topics of 'Nitric oxide synthesis serves to reduce hepatic damage during acute murine endotoxemia'. Together they form a unique fingerprint.

Cite this