Hepatic venous
endothelin-1 was significantly higher in the patients with
cirrhosis, mean 21.2 +/- 0.9 pg/ml (SEM) than in the hypertensive controls, 12.4 +/- 2.4 pg/ml, and normotensive controls, 9.6 +/- 1.6 pg/ml (p < 0.00001). Similarly arterial
endothelin-1 was significantly higher in the patients with
cirrhosis than in the controls (p < 0.00001). Hepatic venous
endothelin-1 was significantly correlated with the hepatic venous pressure gradient (r = 0.61, p < 0.00004), serum
creatinine (r = 0.35, p < 0.03), diastolic blood pressure (r = -0.31, p < 0.05), central and arterial blood volume (-0.36, p < 0.05), central circulation time (r = -0.41, p < 0.02), and serum
sodium (r = -0.56, p < 0.00002) in the patients with
cirrhosis. The hepatosplanchnic release of
endothelin-1, assessed as the arteriohepatic-venous difference adjusted for hepatic plasma flow, was higher in the group with
cirrhosis, 1.5 +/- 0.4 ng/min, than in the normotensive controls, -0.1 +/- 0.2 ng/min (p < 0.01), and was furthermore correlated to the cardiac output in the group with
cirrhosis (r = 0.35, p < 0.04). Hepatic venous
endothelin-3 was higher in the patients with
cirrhosis, 19.0 +/- 1.4 pg/ml (n = 23), as compared with hypertensive controls, 14.2 +/- 1.3 pg/ml, and normotensive controls, 10.0 +/- 1.4 pg/ml (p < 0.002). The same pattern was found in arterial
endothelin-3. Hepatic venous
endothelin-3 correlated significantly with central and arterial blood volume (r = 0.56, p < 0.02). The hepatosplanchnic release of
endothelin-3 was higher in the patients with
cirrhosis, 1.0 +/- 0.7 ng/min, than in the normotensive controls, -0.7 +/- 0.4 ng/min (p = 0.05).
CONCLUSIONS: In the presence of
cirrhosis, hepatic venous and circulating
endothelin-1 and
endothelin-3 are elevated with significant relations to systemic and splanchnic haemodynamics, and the hepatosplanchnic release of both
peptides is increased. This suggests that the
endothelin system is implicated in both systemic and portal haemodynamic abnormalities in
cirrhosis, although this study does not allow conclusions on causal relationships.