ADMA correlates with portal pressure in patients with compensated cirrhosis.
BACKGROUND
Chronic liver diseases are frequently complicated by portal hypertension, an important component of which is the increased intrahepatic vascular resistance, in part related to endothelial dysfunction. Asymmetric dimethylarginine (ADMA), an endogenous inhibitor of NO synthase, is an established mediator and marker of endothelial dysfunction. We therefore investigated the possible implication of ADMA in chronic liver diseases-induced portal hypertension.


METHODS
We studied 39 consecutive patients with compensated hepatitis C virus (HCV) related chronic liver diseases. All patients underwent hepatic venous pressure gradient (HVPG) measurement, and simultaneous blood sampling from the hepatic vein and the pulmonary artery, for ADMA and nitrite/nitrate (NOx) plasma level determinations.


RESULTS
A positive correlation between HVPG and ADMA concentrations in hepatic veins (ADMA-h) was found (r = 0.77, P < 0.0001). Moreover, a negative correlation between HVPG and NOx concentrations in the hepatic veins (NO-h) (r = -0.50, P = 0.005), and between ADMA-h and NO-h was observed (r = -0.40, P = 0.02). ADMA concentrations in pulmonary artery (ADMA-p) (0.55 +/- 0.13 micromol L(-1)) were significantly higher than in hepatic veins (0.47 +/- 0.09 micromol L(-1)) (P < 0.0001).


CONCLUSIONS
These results suggest that ADMA may play a pathophysiological role in portal hypertension by contributing to the relative intrahepatic NO deficiency typical of endothelial dysfunction.
Vizzutti
F
F
Dipartimento di Medicina Interna, Università degli Studi di Firenze, Florence, Italy.
Romanelli
R G
RG
Arena
U
U
Rega
L
L
Brogi
M
M
Calabresi
C
C
Masini
E
E
Tarquini
R
R
Zipoli
M
M
Boddi
V
V
Marra
F
F
Laffi
G
G
Pinzani
M
M
D000328:Adult; D000368:Aged; D001120:Arginine / Q000031:analogs & derivatives* / Q000502:physiology; D016022:Case-Control Studies; D005260:Female; D019698:Hepatitis C, Chronic / Q000150:complications* / Q000503:physiopathology; D006801:Humans; D006975:Hypertension, Portal / Q000209:etiology* / Q000503:physiopathology; D008103:Liver Cirrhosis / Q000503:physiopathology*; D008297:Male; D008875:Middle Aged; D009569:Nitric Oxide / Q000378:metabolism; D017082:Portal Pressure / Q000502:physiology
D009569:Nitric Oxide; C018524:N,N-dimethylarginine; D001120:Arginine