ENDOTHELIN-1 DOES NOT PLAY A MAJOR ROLE IN THE HOMEOSTASIS OF ARTERIAL-PRESSURE IN CIRRHOTIC RATS WITH ASCITES

Background/Aims: Patients with cirrhosis and ascites have increased pl asma levels of endothelin, a powerful vasoconstrictor peptide. This st udy assessed the mechanisms underlying this phenomenon. Methods: Plasm a endothelin was measured in control rats and cirrhotic rats with and without ascites. In addition, the tissue concentration of endothelin a nd 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 endothel in levels were significantly higher in cirrhotic rats with ascites (24 .5 +/- 2.8 pg/mL; P < 0.001) than in cirrhotic rats without ascites an d control rats (7.9 +/- 2.0 and 5.8 +/- 0.9 pg/mL, respectively). In a nimals with ascites, endothelin and endothelin 1 mRNA content in the l ung, kidney, and aorta was similar to that of the controls, in contras t, higher endothelin content (0.567 +/- 0.217 vs. 0.045 +/- 0.002 pg/m g protein; P < 0.05) and endothelin 1 mRNA was observed in hepatic tis sue of rats with cirrhosis and ascites. Endothelin A receptor blockade was not associated with significant changes in arterial and portal pr essure in any group of animals. Conclusions: Increased endothelin 1 mR NA and endothelin production occurs in the livers of cirrhotic rats wi th ascites. In addition, our findings suggest that endothelin is not i nvolved with the homeostasis of arterial or portal pressure in cirrhos is with ascites.