ENDOTHELIN-1 AND ENDOTHELIN-3 IN CIRRHOSIS - RELATIONS TO SYSTEMIC AND SPLANCHNIC HEMODYNAMICS

Background/Aims: Endothelins are isopeptides with potent vasoactive pr operties, but their implications in the hyperkinetic syndrome in cirrh osis are obscure. Therefore, the aim of the present study was to relat e hepatic venous and circulating endothelin-1 and endothelin-3 to syst emic and splanchnic haemodynamics. Methods: Endothelin-1 and endotheli n-3 were measured in samples from a hepatic vein and the femoral arter y in 42 patients with cirrhosis, eight hypertensive controls and 10 no rmotensive controls. Results: Hepatic venous endothelin-l was signific antly higher in the patients with cirrhosis, mean 21.2+/-0.9 pg/ml (SE M) than in the hypertensive controls, 12.4+/-2.4 pg/ml, and normotensi ve controls, 9.6+/-1.6 pg/ml (p<0.00001). Similarly arterial endotheli n-l was significantly higher in the patients with cirrhosis than in th e controls (p<0.00001). Hepatic venous endothelin-l was significantly correlated with the hepatic venous pressure gradient (r=0.61, p<0.0000 4), 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), centra l 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 adjust ed 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 gr oup with cirrhosis (r=0.35, p<0.04). Hepatic venous endothelin-3 was h igher in the patients with cirrhosis, 19.0+/-1.4 pg/ml (n=23), as comp ared with hypertensive controls, 14.2+/-1.3 pg/ml, and normotensive co ntrols, 10.0+/-1.4 pg/ml (p<0.002). The same pattern was found in arte rial endothelin-3. Hepatic venous endothelin-3 correlated significantl y with central and arterial blood volume (r=0.56, p<0.02). The hepatos planchnic release of endothelin-3 was higher in the patients with cirr hosis, 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 v enous and circulating endothelin-l and endothelin-3 are elevated with significant relations to systemic and splanchnic haemodynamics, and th e hepatosplanchnic release of both peptides is increased. This suggest s 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.