NITRIC-OXIDE SYNTHASE ISOFORM-III GENE-EXPRESSION IN RAT-LIVER IS UP-REGULATED BY LIPOPOLYSACCHARIDE AND LIPOTEICHOIC ACID

This study was done to investigate the influence of Gram-negative and Gram-positive sepsis on the expression of the three isoforms of nitric oxide synthase (NOS) gene in rat liver and kidney, Male Sprague-Dawle y rats mere treated with lipopolysaccharide (LPS, 10 mg/kg i,v,) as an in vivo model for Gram-negative sepsis or lipoteichoic acid (LTA, 10 mg/kg i,v,) as an in vivo model for Gram-positive sepsis, Animals were killed 12 h and 24 h after i,v, treatment, NOS mRNA of the three isof orms was determined by RNase protection assay, NOS II gene expression was strongly induced after LPS or LTA treatment in rat liver and kidne y, indicating the efficacy of this treatment to induce sepsis, We foun d no change of NOS I gene expression after LPS or LTA injection in rat liver and kidney. NOS III gene expression was increased about 8-fold 12 h and about 5-fold 24 h after induction of sepsis in the rat liver whereas in the kidney there was no significant increase in NOS III gen e expression. After correction for length NOS III mRNA was about 4- an d 10-fold more abundant 12 h and 24 h after LPS treatment than NOS II mRNA in the liver, respectively, Twelve and 24 h after LTA treatment N OS III mRNA was about 18- and and 140-fold more abundant than NOS II i n the liver, These findings suggest that NOS III is an even more poten t source of NO than NOS II in the liver after stimulation with LPS or LTA. (C) 1997 Federation of European Biochemical Societies.