Effects of intravenous nitric oxide inhibitors on endotoxin-induced fever in prepubertal pigs.

1. The ability of nitric oxide inhibitors to antagonize the febrile effects of lipopolysaccharide (LPS) endotoxin (20 microg/animal i.v.) was assessed in prepubertal pigs in which deep body temperature was measured at 10-min intervals for 180 min. 2. In experiment 1, pigs (n=5) were injected with Nomega-nitro-L-arginine-methyl ester (L-NAME) (30 mg/kg i.v.) or aminoguanidine (27 mg/kg i.v.) 30 min before LPS. There was a marked tendency for L-NAME, but not aminoguanidine, to reduce LPS pyrexia. 3. In experiment 2, pigs (n=7) were injected with 2-amino-4-methylpyridine (1 mg/kg i.v.) 30 min before LPS. This drug tended to increase, rather than reduce, core temperature. 4. In experiment 3, pigs (n=5) were injected with S-methylisothiourea (10 or 15 mg/kg i.v.) concomitantly with LPS. Both doses of the drug produced a small, nonsignificant, reduction in the febrile response. 5. The results indicate that the nitric oxide inhibitors used in this study were relatively ineffective in modifying LPS fever in conscious pigs; these findings are in marked contrast with the actions, in this species, of drugs that inhibit prostaglandin production. In addition, the most effective drug, L-NAME, was the one considered to be the least selective for the inducible form of nitric oxide.