Nitric oxide may upregulate in vivo hepatic protein synthesis during endotoxemia.
Nitric oxide (NO) has been implicated as a mediator of hemodynamic and metabolic changes associated with endotoxemia and inflammation. In vitro studies suggest that NO inhibits hepatocyte protein synthesis but the role of NO in the regulation of hepatic protein synthesis in vivo is not known. In this study, rats were given endotoxin or saline after pretreatment with the NO synthase inhibitor NG-nitro-L-arginine or solvent, and plasma levels of nitrite (NO2), nitrate (NO3), and aspartate aminotransferase and hepatic protein synthesis rate in vivo were measured after 4 and 10 hours. The NG-nitro-L-arginine effectively blocked the increase in serum NO2/NO3 seen in endotoxemia and also inhibited the increase in hepatic protein synthesis in endotoxemic rats. The aspartate aminotransferase levels were elevated in endotoxemic rats pretreated with NG-nitro-L-arginine. Results support previous reports of a protective effect of NO on the liver in endotoxemia and suggest that NO may upregulate hepatic protein synthesis in vivo. Further study is needed to clarify the reason for the apparent difference between the effect of NO on hepatic protein synthesis in vivo and in vitro.
Frederick
J A
JA
Department of Surgery, University of Cincinnati, Ohio.
Hasselgren
P O
PO
Davis
S
S
Higashiguchi
T
T
Jacob
T D
TD
Fischer
J E
JE
D000594:Amino Acid Oxidoreductases / Q000037:antagonists & inhibitors; D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives* / Q000494:pharmacology; D001219:Aspartate Aminotransferases / Q000097:blood; D002250:Carbon Radioisotopes; D004731:Endotoxins / Q000008:administration & dosage / Q000097:blood*; D007930:Leucine / Q000378:metabolism; D008099:Liver / Q000187:drug effects* / Q000378:metabolism* / Q000473:pathology; D008297:Male; D009566:Nitrates / Q000097:blood; D009569:Nitric Oxide / Q000494:pharmacology*; D019001:Nitric Oxide Synthase; D009573:Nitrites / Q000097:blood; D019335:Nitroarginine; D014176:Protein Biosynthesis; D051381:Rats; D017207:Rats, Sprague-Dawley; D015854:Up-Regulation / Q000187:drug effects
D002250:Carbon Radioisotopes; D004731:Endotoxins; D009566:Nitrates; D009573:Nitrites; D019335:Nitroarginine; D009569:Nitric Oxide; D001120:Arginine; D019001:Nitric Oxide Synthase; D000594:Amino Acid Oxidoreductases; D001219:Aspartate Aminotransferases; D007930:Leucine