Background/aims: Patients with cirrhosis and ascites have increased plasma levels of endothelin, a powerful vasoconstrictor peptide. This study assessed the mechanisms underlying this phenomenon.
Methods: Plasma endothelin was measured in control rats and cirrhotic rats with and without ascites. In addition, the tissue concentration of endothelin and endothelin 1 messenger RNA (mRNA) and the effect of an endothelin A receptor antagonist on arterial and portal pressure were assessed in cirrhotic rats with ascites and control rats.
Results: Plasma endothelin levels were significantly higher in cirrhotic rats with ascites (24.5 +/- 2.8 pg/mL; P < 0.001) than in cirrhotic rats without ascites and control rats (7.9 +/- 2.0 and 5.8 +/- 0.9 pg/mL, respectively). In animals with ascites, endothelin and endothelin 1 mRNA content in the lung, kidney, and aorta was similar to that of the controls. In contrast, higher endothelin content (0.567 +/- 0.217 vs. 0.045 +/- 0.002 pg/mg protein; P < 0.05) and endothelin 1 mRNA was observed in hepatic tissue of rats with cirrhosis and ascites. Endothelin A receptor blockade was not associated with significant changes in arterial and portal pressure in any group of animals.
Conclusions: Increased endothelin 1 mRNA and endothelin production occurs in the livers of cirrhotic rats with ascites. In addition, our findings suggest that endothelin is not involved with the homeostasis of arterial or portal pressure in cirrhosis with ascites.