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 ester (L-NAME), an unspecific nitric oxide synthase (NOS) inhibitor, and aminoguanidine, a relatively selective inhibitor of the inducible NOS enzyme, on both gram-negative lipopolysaccharide (LPS) and gram-positive muramyl dipeptide (MDP) fever in guinea pigs. Intraperitoneal injection of either 10 mg/kg L-NAME or 25 mg/kg aminoguanidine inhibited the febrile response to an intramuscular injection of 50 microg/kg MDP. However, LPS fever (20 microg/kg) was inhibited only by L-NAME. The development of LPS fever may therefore occur independently of the synthesis of nitric oxide by the inducible NOS enzyme, while MDP fever may involve synthesis of nitric oxide by both the inducible and the constitutively expressed NOS enzymes.
Kamerman
P
P
Department of Physiology, University of the Witwatersrand, Medical School, Parktown, Johannesburg, South Africa. 127ned@chiron.wits.ac.za
Fuller
A
A
D000005:Abdomen; D000119:Acetylmuramyl-Alanyl-Isoglutamine / Q000633:toxicity*; D000818:Animals; D006224:Cricetinae; D004791:Enzyme Inhibitors / Q000627:therapeutic use*; D004926:Escherichia coli; D005260:Female; D005334:Fever / Q000139:chemically induced / Q000188:drug therapy* / Q000201:enzymology; D006146:Guanidines / Q000008:administration & dosage / Q000627:therapeutic use*; D006168:Guinea Pigs; D007273:Injections, Intramuscular; D008070:Lipopolysaccharides / Q000633:toxicity*; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000008:administration & dosage / Q000627:therapeutic use*; D009569:Nitric Oxide / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors*; D052247:Nitric Oxide Synthase Type II
D004791:Enzyme Inhibitors; D006146:Guanidines; D008070:Lipopolysaccharides; D009569:Nitric Oxide; D000119:Acetylmuramyl-Alanyl-Isoglutamine; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C004479:pimagedine; D019331:NG-Nitroarginine Methyl Ester