Modulation of nitrogen oxide synthesis in vivo: NG-monomethyl-L-arginine inhibits endotoxin-induced nitrate/nitrate biosynthesis while promoting hepatic damage.
Attempts were made to promote or inhibit nitric oxide (. N = O) synthesis in a murine model of hepatic damage (Corynebacterium parvum followed by lipopolysaccharide; LPS) to determine the role of . N = O in the liver injury. Moderate hepatic damage and increases in circulating NO2-/NO3- levels were detectable after C. parvum alone. Administration of LPS to these mice resulted in severe hepatic damage and acute elevations in circulating nitrogen oxide levels. L-arg had no influence on the C. parvum or LPS-induced changes. NG-monomethyl-L-arginine (NMA) had no effect in the absence of LPS, but when given with LPS, a dose-dependent suppression in plasma NO2-/NO3- levels and an increase in liver injury were seen. The NMA-induced changes were partially reversed by the simultaneous administration of L-arg. These findings suggest a protective role for . N = O in this model.
Billiar
T R
TR
Department of Surgery, University of Pittsburgh, PA 15261.
Curran
R D
RD
Harbrecht
B G
BG
Stuehr
D J
DJ
Demetris
A J
AJ
Simmons
R L
RL
D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives* / Q000494:pharmacology; D005260:Female; D008070:Lipopolysaccharides / Q000633:toxicity*; D008099:Liver / Q000187:drug effects* / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D009566:Nitrates / Q000378:metabolism*; D009573:Nitrites / Q000378:metabolism*; D009589:Nitrogen Oxides / Q000378:metabolism*; D011425:Propionibacterium acnes / Q000472:pathogenicity; D019323:omega-N-Methylarginine
D008070:Lipopolysaccharides; D009566:Nitrates; D009573:Nitrites; D009589:Nitrogen Oxides; D019323:omega-N-Methylarginine; D001120:Arginine