Objective : It has been recently known that endotheUn-1 is a potent vasoconstrictor. The purpose of the present study was to clarify the possible correlation of endothelin-1 with other vasoactive neurohormonal activities and its effects on fluid-electrolyte balance and renal function in patients with liver cirrhosis.
Methods : In 35 patients of liver cirrhosis with (n=19) and without (n=16) ascites and in 12 normal controls, plasma and urine levels of endothelin-1 were measured by specific radioimmunoassay, and serum sodium, serum albumin and other blood chemistries, renal functions with creatinine clearance, urinary sodium excretion, plasma renin activity, plasma aldosterone and plasma norepinephrine were measured at the same time.
Results : The plasma endothelin-1 level was significantly higher in ascitic group than nonascitic group (mean +/- SD; 16.4 +/- 10.6 VS. 7.5 +/- 4.1pg/mL, p=0.0000), and there was no significant difference in plasma endothelin-1 level between nonascitic group and normal controls(4.8 +/- 1.9pg/mL). The urine endothelin-1 level also was significantly higher in ascitic group than non-ascitic group (140.3 +/- 74.3 VS. 58.5 +/- 37.4 pg/mL, p=0.0000), there was no significant difference in urine endothelin-1 level between nonascitic group and normal controls (19.5 +/- 112pg/mL). In patients with cirrhosis, the plasma endothelin-1 concentration showed significant negative correlation with creatinine clearance (r=-0.55), serum albumin (r=-0.56%) and serum sodium concentrtion (r=-0.62), and significant positive correlation with plasma renin activity (r=0.63), plasma aldosterone (r=0.68) and norepinephrine (r=0.70). The factors that influence on plasma concentration of endothelin-1 were plasma norepinephrine (p=0.0000), serum sodium (p=0.0169), plasma aldosterone (p=0.0176), serum albumin (p=0.0213) and plasma renin activity (p=0.0329) in statistically significant order.
Conclusion : The elevated plasma endothelin-1 level along with the increased activity of other neurohormonal substances including plasma renin, aldosterone and norepinephrine induces sodium and water retention in decompensated liver cirrhosis. Thus, the plasma endothelin-1 level seems to have an important role in the development of functional renal impairment in decompensated liver cirrhosis by inducing renal vasoconstriction.
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