Conservation of whole body nitric oxide metabolism in human alcoholic liver disease: implications for nitric oxide production

DEMONCHEAUX, E. A. G., ELPHICK, D. A., DURNER, M. B., HIGGINS, G. E., CROWTHER, D., WILLIAMS, E. J., HIGENBOTTAM, T. W. and GLEESON, D. (2005). Conservation of whole body nitric oxide metabolism in human alcoholic liver disease: implications for nitric oxide production. Scandinavian journal of gastroenterology, 41 (7), 820-825.

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Link to published version:: 10.1080/00365520500442724

Abstract

Objective. Patients with advanced liver diseases tend to develop a hyperdynamic circulation which complicates cirrhosis. Impairment of nitric oxide (NO) metabolism has been implicated in the pathogenesis of portal hypertension. The aim of this study was to determine nitric oxide synthase (NOS)-dependent whole body NO production in patients with decompensated liver cirrhosis and portal hypertension. Material and methods. Ten patients with decompensated alcoholic liver disease and portal hypertension (Child-Pugh Classifications B and C with no signs of infection) and 10 age- and gender-matched control subjects received an intravenous infusion of L-[15N]2-arginine (50 µmol/min for 30 min). Urine and serum nitrite and nitrate concentrations were determined using ion chromatography-mass spectrometry. Results. NOS-dependent whole body NO synthesis was estimated by the conversion of [15N]guanidino nitrogen of arginine to urine 15N-nitrite and 15N-nitrate. The amount of 15N-nitrite and 15N-nitrate in the urine of patients and control subjects was significantly correlated with the amount of urine nitrite and nitrate over 36 h (r=0.91 and 0.77, respectively, p<0.0001). However, neither a median of 12 h 15N-nitrite and 15N-nitrate nor nitrite and nitrate excretion in the urine was different between patients and control subjects, 46.4 (9.4-152.2) versus 98.7 (29.9-146.5) nmol/mmol creatinine and 20.6 (2.1-69.0) versus 40.0 (27.0-70.1) µmol/mmol creatinine, respectively. No differences were found in serum nitrite and nitrate concentrations and glomerular filtration rates between patients and control subjects, 111.4 (73.2-158.8) versus 109.3 (83.5-176.4) µmol/l. Conclusion. Our results contraindicate a greater basal NOS-dependent whole body NO production in patients with decompensated liver disease and portal hypertension.

Item Type: Article
Research Institute, Centre or Group: Biomedical Research Centre
Identification Number: 10.1080/00365520500442724
Depositing User: Ann Betterton
Date Deposited: 10 Mar 2008
Last Modified: 09 Dec 2009 18:23
URI: http://shura.shu.ac.uk/id/eprint/416

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