Role of nitric oxide pathway in the protection against lethal endotoxemia afforded by low doses of lipopolysaccharide.
Survival after lipopolysaccharide challenge (LD80, 20 mg.kg-1, i.p.) was significantly enhanced by previous treatment with a microdose of LPS (50 micrograms.kg-1, i.v.). When NG-monomethyl-L-arginine, a specific inhibitor of the formation of nitric oxide from L-arginine, was given 30 minutes before microdose, survival was significantly reduced. When we monitored the serum Tumor Necrosis Factor (TNF) levels in both groups a significant reduction of TNF level after the microdose was observed in mice previously treated with L-NMMA. The ability of L-NNMA to reduce TNF release was dose dependent.
Rojas
A
A
Center for Pharmaceutical Chemistry, Havana, Cuba.
Padrón
J
J
Caveda
L
L
Palacios
M
M
Moncada
S
S
D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000378:metabolism / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D008070:Lipopolysaccharides / Q000008:administration & dosage / Q000627:therapeutic use* / Q000633:toxicity; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009569:Nitric Oxide / Q000378:metabolism*; D018805:Sepsis / Q000209:etiology / Q000378:metabolism / Q000517:prevention & control*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D019323:omega-N-Methylarginine
D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha; D019323:omega-N-Methylarginine; D009569:Nitric Oxide; D001120:Arginine