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


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 micromol/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) micromol/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) micromol/l.


CONCLUSIONS
Our results contraindicate a greater basal NOS-dependent whole body NO production in patients with decompensated liver disease and portal hypertension.
Demoncheaux
Eric A G
EA
Division of Clinical Sciences, University of Sheffield, The Royal Hallamshire Hospital, Sheffield, UK. eric_demoncheaux@yahoo.co.uk
Elphick
David A
DA
Dürner
Marc B
MB
Higgins
Gail E
GE
Crowther
David
D
Williams
Earl J
EJ
Higenbottam
Tim W
TW
Gleeson
Dermot
D
D001120:Arginine / Q000378:metabolism; D016022:Case-Control Studies; D005260:Female; D006801:Humans; D006975:Hypertension, Portal / Q000139:chemically induced / Q000378:metabolism*; D008099:Liver / Q000201:enzymology; D008104:Liver Cirrhosis, Alcoholic / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D009569:Nitric Oxide / Q000378:metabolism*; D019001:Nitric Oxide Synthase / Q000378:metabolism; D009587:Nitrogen Isotopes / Q000378:metabolism
D009587:Nitrogen Isotopes; D009569:Nitric Oxide; D001120:Arginine; D019001:Nitric Oxide Synthase