Endothelin-1 and endothelin-3 in cirrhosis: relations to systemic and splanchnic haemodynamics.

BACKGROUND/AIMS: Endothelins are isopeptides with potent vasoactive properties, but their implications in the hyperkinetic syndrome in cirrhosis are obscure. Therefore, the aim of the present study was to relate hepatic venous and circulating endothelin-1 and endothelin-3 to systemic and splanchnic haemodynamics.
METHODS: Endothelin-1 and endothelin-3 were measured in samples from a hepatic vein and the femoral artery in 42 patients with cirrhosis, eight hypertensive controls and 10 normotensive controls.
RESULTS: 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.