ELEVATED CIRCULATING PLASMA ENDOTHELIN-1 CONCENTRATIONS IN CIRRHOSIS

As endothelin-1 (ET-1), a potent vasoconstricting peptide, may play a role in the circulatory derangement and renal impairment in cirrhosis, the aim of the present study was to investigate plasma concentrations of ET-1 in different vascular beds in relation to clinical and biochemical parameters of liver function. Median brachial venous ET-1 concentrations were substantially higher in patients with cirrhosis (3.40 pg/ml, range: 1.25-7.84, n = 24) than in controls (1.53 pg/ml, range: 0.78-2.12, n = 11)(P < 0.00005). In patients with cirrhosis ET-1 was directly correlated to serum creatinine (r = 0.70, P < 0.0001) and aspartate aminotransferase (r = 0.44, P < 0.03) and negatively correlated to serum sodium (r = -0.58, P < 0.003). In patients who underwent liver vein catheterization (n = 8), no significant differences were found in ET-1 plasma concentrations between the liver, renal, or femoral veins on the one hand and the femoral artery on the other (P > 0.1), indicating no major net elimination or release in the liver, kidney or lower limb. A significant negative correlation was found between systolic and diastolic blood pressures on the one hand and circulating ET-1 on the other (r = -0.71, P < 0.05). In conclusion, circulating ET-1 is elevated in cirrhosis and related to markers of systemic circulation and renal function, thus suggesting a role for ET-1 in the circulatory derangement and nephropathy in cirrhosis. Locations of major net elimination or release of ET-1 were not identified.