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.
Parrott
R F
RF
MAFF Welfare and Behaviour Laboratory, Department of Neurobiology, Babraham Institute, Cambridge, United Kingdom.
Vellucci
S V
SV
Lloyd
D M
DM
D000818:Animals; D004731:Endotoxins; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005334:Fever / Q000139:chemically induced / Q000517:prevention & control*; D006146:Guanidines / Q000494:pharmacology; D007550:Isothiuronium / Q000031:analogs & derivatives / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000494:pharmacology; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology*; D009569:Nitric Oxide / Q000037:antagonists & inhibitors* / Q000502:physiology; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D052247:Nitric Oxide Synthase Type II; D013552:Swine
D004731:Endotoxins; D004791:Enzyme Inhibitors; D006146:Guanidines; D008070:Lipopolysaccharides; D007550:Isothiuronium; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C027744:S-methylisothiopseudouronium; C004479:pimagedine; D019331:NG-Nitroarginine Methyl Ester