This study was supported by the National Institute of Health Grant AA 09803 and by the National Science Foundation/LaSER RCD 02 grant from the Louisiana Board of Regents.
Chronic Alcohol Administration Stimulates Nitric Oxide Formation in the Rat Liver With or Without Pretreatment by Lipopolysaccharide
Version of Record online: 11 APR 2006
Alcoholism: Clinical and Experimental Research
Volume 19, Issue 2, pages 387–393, April 1995
How to Cite
Wang, J.-F., Greenberg, S. S. and Spitzer, J. J. (1995), Chronic Alcohol Administration Stimulates Nitric Oxide Formation in the Rat Liver With or Without Pretreatment by Lipopolysaccharide. Alcoholism: Clinical and Experimental Research, 19: 387–393. doi: 10.1111/j.1530-0277.1995.tb01520.x
- Issue online: 11 APR 2006
- Version of Record online: 11 APR 2006
- Received for publication July 7, 1994; accepted October 12, 1994
- Reactive Nitrogen Intermediates (RNI);
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 supematants 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 μm (mean ×se). Livers from diet-fed control rats produced RNIs at the barely detectable rate of 7.8 ± 1.5 nmol/hr × g wet liver. Six hr after administration of LPS (1 mg/kg, iv), plasma RNI levels in diet-fed control rats increased to 426.9 ± 29.4 μm, and RNI release from the perfused liver was also markedly elevated to 97.7 ± 7.7 nmol/hr × 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. Chronic alcohol administration resulted in increased RNI levels in plasma (44.6 ± 4.2) that were accompanied by increased spontaneous release in the perfused liver (16.4 ± 1.5 nmol/hr wet g). Enhanced activity of Kupffer cells was responsible for this increase. After administration of LPS, the increase in plasma RNIs (565.72 ± 49.6 μm) was slightly higher in chronic alcoholic rats than in control animals. This was also accompanied by a somewhat higher RNI release from the perfused liver (125.40 ± 12.2 nmol/hr × wet g) in the same group. Hepatocytes were responsible for the post-LPS increase in alcoholic rats. Plasma ALT concentration was higher in alcoholic than control, diet-fed rats after LPS, indicating more liver damage in that group. The exact role of the elevated hepatic RNI release in affecting hepatic function in chronic alcoholic animals remains to be clarified.