Does upregulation of inducible nitric oxide synthase play a role in hepatic injury?

Shock. 2002 Dec;18(6):549-54. doi: 10.1097/00024382-200212000-00011.


Lipopolysaccharide (LPS) and gut ischemia/reperfusion (I/R) injury cause reversible liver injury. Because nitric oxide (NO) can have both beneficial and deleterious effects in the gastrointestinal tract, and because the role of NO in gut I/R-induced hepatic injury is unknown, this study examined its role in LPS and gut I/R-induced hepatic injury in the rat. Both LPS and gut I/R caused a similar increase in serum hepatocellular enzymes. LPS but not gut I/R caused a significant increase in upregulation of hepatic inducible NO synthase (iNOS) according to quantitative real-time RT-PCR and Western immunoblot analysis. Aminoguanidine, a selective iNOS inhibitor, attenuated LPS-induced hepatic injury and hypotension, but did not prevent gut I/R-induced hepatic injury. In contrast, the non-selective NOS inhibitor N(G)-nitro-L-arginine methyl ester aggravated liver damage from both LPS and gut I/R. These data indicate that iNOS plays a role in mediating LPS-induced hepatic injury, but not gut I/R-induced hepatic injury. The data also suggest that the constitutive isoforms of NOS play a hepatoprotective role in both models of hepatic injury.

Publication types

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

MeSH terms

  • Anesthetics / pharmacology
  • Animals
  • Aspartate Aminotransferases / metabolism
  • Blotting, Western
  • Enzyme Induction* / drug effects
  • Female
  • Injections, Intraperitoneal
  • Lipopolysaccharides / pharmacology
  • Liver / enzymology*
  • Liver / pathology*
  • NG-Nitroarginine Methyl Ester / pharmacology
  • Nitric Oxide Synthase / metabolism*
  • Nitric Oxide Synthase Type II
  • Rats
  • Rats, Sprague-Dawley
  • Up-Regulation / drug effects


  • Anesthetics
  • Lipopolysaccharides
  • Nitric Oxide Synthase
  • Nitric Oxide Synthase Type II
  • Nos2 protein, rat
  • Aspartate Aminotransferases
  • NG-Nitroarginine Methyl Ester