Plasma concentrations of nitric oxide and asymmetric dimethylarginine in human alcoholic cirrhosis.
OBJECTIVE
The liver plays a prominent role in the metabolism of asymmetric dimethyl-l-arginine (ADMA), an endogenous inhibitor of nitric oxide (NO) synthase. This study was designed to determine whether plasma levels of ADMA and NO production are altered in patients with compensated and decompensated alcoholic cirrhosis.


METHODS
Plasma levels of l-arginine, ADMA, symmetric dimethylarginine (SDMA) and NO (nitrite plus nitrate, NOx) were measured in nine patients with compensated alcoholic cirrhosis (Child-Pugh A) and 11 patients with advanced cirrhosis (Child-Pugh B-C). Seven healthy volunteers served as controls.


RESULTS
ADMA and NOx concentrations in decompensated cirrhosis were higher than in the compensated group and control group (ADMA: 1.12+/-0.08 vs. 0.58+/-0.05 and 0.58+/-0.07micromol/l, respectively; P<0.05; NOx 97.90+/-10.27 vs. 37.42+/-3.91 and 40.43+/-5.30micromol/l, respectively; P<0.05). There was a positive correlation between the clinical score of the patients and concentrations of ADMA (r(2)=0.547, P<0.01) and NOx (r(2)=0.689, P<0.01). SDMA and l-arginine levels were not significantly different between the three groups.


CONCLUSIONS
The results suggest that hepatocellular damage is a main determinant of elevated ADMA concentration in advanced alcoholic cirrhosis. By inhibiting NO release from vascular endothelium, ADMA might oppose the peripheral vasodilation caused by excessive NO production in severe cirrhosis.
Lluch
Paloma
P
Servicio de Hepatología, Hospital Clínico Universitario, Departamento de Medicina, Universidad de Valencia, Blasco Ibañez 17, 46010 Valencia, Spain. lluchs@post.uv.es
Torondel
Belén
B
Medina
Pascual
P
Segarra
Gloria
G
Del Olmo
Juan A
JA
Serra
Miguel A
MA
Rodrigo
José M
JM
D001120:Arginine / Q000031:analogs & derivatives* / Q000097:blood*; D004730:Endothelium, Vascular / Q000378:metabolism; D005260:Female; D006801:Humans; D008104:Liver Cirrhosis, Alcoholic / Q000097:blood* / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D009566:Nitrates / Q000097:blood; D009569:Nitric Oxide / Q000097:blood*; D009573:Nitrites / Q000097:blood; D014664:Vasodilation / Q000502:physiology
D009566:Nitrates; D009573:Nitrites; C487735:dimethylarginine; D009569:Nitric Oxide; C018524:N,N-dimethylarginine; D001120:Arginine