Effects of nitric oxide synthase inhibitors on the febrile response to lipopolysaccharide and muramyl dipeptide in guinea pigs

We investigated the effect of N-nitro-L-arginine methyl eater (L-NAME), an unspecific nitric oxide synthase (NOS) inhibitor, and aminoguanidine, a rel atively selective inhibitor of the inducible NOS enzyme, on both Gram-negat ive lipopolysaccharide (LPS) and Gram-positive muramyl dipeptide (MDP) feve r in guinea pigs. Intraperitoneal injection of either 10 mg/kg L-NAME or 25 mg/kg aminoguanidine inhibited the febrile response to an intramuscular in jection of 50 mu g/kg MDP. However, LPS fever (20 mu g/kg) was inhibited on ly by L-NAME. The development of LPS fever may therefore occur independentl y of the synthesis of nitric oxide by the inducible NOS enzyme, while MDP f ever may involve synthesis of nitric oxide by both the inducible and the co nstitutively expressed NOS enzymes. (C) 2000 Elsevier Science Inc. All righ ts reserved.