Effects of inhibition of nitric oxide synthesis on TNF alpha serum levels in E. coli endotoxemic rats.

We investigated the effects of nitric oxide (NO) synthesis inhibition on mortality rate and TNF alpha serum levels in rats inoculated with E. Coli endotoxin (30 mg/kg i.v.) Pre-treatment of endotoxemic rats with NG-monomethyl-L-arginine (L-NMMA), an inhibitor of NO synthesis by both the constitutive and the inducible isoforms of the NO synthase, did not change the mortality rate but significantly reduced TNF alpha serum levels. By contrast, administration of aminoguanidine, a more specific inhibitor of the inducible NO synthase, did not modify serum TNF alpha. These results suggest that, in E. Coli endotoxemic rats, NO synthetized by the constitutive isoform of the NO synthase positively modulates TNF alpha synthesis.