Ursodeoxycholic acid reduces increased circulating endothelin 2 in primary biliary cirrhosis.
BACKGROUND
Endothelins and nitric oxide regulate sinusoidal blood flow and the perfusion of the peribiliary vascular plexus.


OBJECTIVE
To study the serum and hepatic vein concentration of ET-1, ET-2, ET-3 and nitric oxide in patients with primary biliary cirrhosis and the effect of ursodeoxycholic acid treatment.


METHODS
Endothelins and nitrites/nitrates were measured in serum and hepatic vein blood in primary biliary cirrhosis and viral cirrhotic patients prior and after ursodeoxycholic acid therapy and in serum in controls. Endothelins were measured with commercial enzyme-linked immunosorbent assays and nitrites/nitrates with a modification of Griess reaction.


RESULTS
The ET-1 and ET-3 levels were similar in patients and controls. Primary biliary cirrhosis patients had the highest serum ET-2 (P < 0.001) compared with other groups. Nitrites/nitrates was increased in primary biliary cirrhosis (P < 0.05) compared with normal. ET-2 and nitric oxide were similar in all primary biliary cirrhosis stages. Ursodeoxycholic acid significantly decreased ET-2 in all stages (I and II: P < 0.05 and III and IV: P < 0.01) and increased nitric oxide (P < 0.05) in early primary biliary cirrhosis. Hepatic vein ET-1 and ET-3 were higher in viral cirrhosis patients, but only in primary biliary cirrhosis a significant difference for ET-1 and ET-3 between hepatic and peripheral veins was found.


CONCLUSIONS
Increased ET-2 is an early defect in primary biliary cirrhosis that is significantly reduced by the ursodeoxycholic acid treatment. The possibility of a more generalized endothelial cell dysfunction in primary biliary cirrhosis requires further investigation.
Dimoulios
P
P
Department of Gastroenterology, University Hospital Heraklion and Liver Research Laboratory of University of Heraklion, Crete, Greece.
Kolios
G
G
Notas
G
G
Matrella
E
E
Xidakis
C
C
Koulentaki
M
M
Tsagarakis
N
N
Kouroumalis
A
A
Kouroumalis
E
E
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000704:Analysis of Variance; D002756:Cholagogues and Choleretics / Q000627:therapeutic use*; D019332:Endothelin-1 / Q000097:blood; D019333:Endothelin-2 / Q000097:blood*; D019334:Endothelin-3 / Q000097:blood; D005260:Female; D006503:Hepatic Veins; D006801:Humans; D008105:Liver Cirrhosis, Biliary / Q000097:blood / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D009569:Nitric Oxide / Q000097:blood; D014580:Ursodeoxycholic Acid / Q000627:therapeutic use*
D002756:Cholagogues and Choleretics; D019332:Endothelin-1; D019333:Endothelin-2; D019334:Endothelin-3; D009569:Nitric Oxide; D014580:Ursodeoxycholic Acid