Chronic alcohol administration stimulates nitric oxide formation in the rat liver with or without pretreatment by lipopolysaccharide.
This study examines the effect of chronic alcohol consumption on nitric oxide release from the liver of rats with or without lipopolysaccharide (LPS) (Escherichia coli) treatment. Reactive nitrogen intermediates (RNIs) in plasma were monitored with an NOx Analyzer, and nitric oxide (NO) production was measured as nitrite or nitrite + nitrate accumulation in perfusates of the perfused liver, and in supernatants of the freshly isolated hepatic cells after incubation for 3 hr in Hank's balanced salt solution buffer containing 1 mM L-arginine. RNI concentration in plasma of control rats was 32.0 +/- 3.4 microM (mean +/- SE). Livers from diet-fed control rats produced RNIs at the barely detectable rate of 7.8 +/- 1.5 nmol/hr x g wet liver. Six hr after administration of LPS (1 mg/kg, i.v.), plasma RNI levels in diet-fed control rats increased to 426.9 +/- 29.4 microM, and RNI release from the perfused liver was also markedly elevated to 97.7 +/- 7.7 nmol/hr x wet g liver, indicating hepatic NO release as a potentially important source for the increased RNI in plasma. The presence of NG-monomethyl-L-arginine (0.5-1 mM) or the absence of L-arginine in the perfusate inhibited LPS-induced stimulation of RNI release. EGTA (1 mM) had little effect, indicating that the increased RNI release was likely to be due to inducible NO synthase activity. The release of RNIs by freshly isolated Kupffer cells increased 13-fold, and this small cell mass contributed almost half of the hepatic RNI production under these conditions. Plasma ALT concentration was elevated after LPS administration, indicating incipient liver damage.(ABSTRACT TRUNCATED AT 250 WORDS)
Wang
J F
JF
Department of Physiology, Louisiana State University Medical Center, New Orleans, USA.
Greenberg
S S
SS
Spitzer
J J
JJ
D000594:Amino Acid Oxidoreductases / Q000502:physiology; D000818:Animals; D046508:Culture Techniques; D004790:Enzyme Induction / Q000502:physiology; D004926:Escherichia coli; D000431:Ethanol / Q000633:toxicity*; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008099:Liver / Q000187:drug effects* / Q000503:physiopathology; D008108:Liver Diseases, Alcoholic / Q000503:physiopathology*; D008297:Male; D009569:Nitric Oxide / Q000097:blood*; D019001:Nitric Oxide Synthase; D010477:Perfusion; D051381:Rats; D017207:Rats, Sprague-Dawley
D008070:Lipopolysaccharides; D009569:Nitric Oxide; D000431:Ethanol; D019001:Nitric Oxide Synthase; D000594:Amino Acid Oxidoreductases