Relation of endothelins to volume regulating neurohumoral systems in patients with cirrhosis of the liver

Abstract. The aim of the present study was to investigate the relationship between ET plasma concentrations and other hormonal systems in acute volume regulation of patients with cirrhosis. Ten healthy controls and 10 cirrhotic patients, five without and five with ascites were studied after 1 h in a sitting posture and subsequently subjected to 1 h head-out water immersion. Blood was collected for determinations of ET-1, ET-3, ANF, aldosterone, renin activity and noradrenaline. In addition, in 10 patients with compensated cirrhosis the effect of loop diuretics on ET-3, aldosterone and renin was studied. ETs in cirrhosis were significantly (P<0.01) higher than in controls both before (ET-1, 19.6 ± 1.3pgmL^-1 vs. 11.8 ± 0.4pgmL^-1; ET-3, 18.5±1.4pgmL^-1 vs. 9.5 ± 0.5 pgmL^-1) and after water immersion (ET-1, 18.6± 1.2 pgmL^-1 vs. 12.4±0.3 pgmL^-1; ET-3,18.7 ± 1.7pgmL^-1 vs. 10.0±0.5pg mL^-1). In cirrhotic patients, basal and immersion concentrations of ET-1 were significantly correlated to noradrenaline plasma concentrations (r= 0.79, P<0.05). ET-3 plasma concentrations in cirrhosis were correlated to renin activity (r= 0.65, P<0.05). Furthermore, ET-3 in cirrhosis was inversely correlated to systolic and mean arterial blood pressure (r= -0.55, P<0.01 and r= -0.50, P<0.05, respectively). To investigate the effect of hypovolaemia in compensated cirrhosis, 10 patients without ascites were studied before and after treatment with loop diuretics. In compensated cirrhosis ET-3 was significantly increased 6h after oral diuretic treatment (17.9 ± 1.0 pgmL^-1 vs. 15.5±0.4pg mL^-1, P< 0.001). The presented data demonstrate relations of endothelins, particularly of ET-3 to neurohumoral systems in patients with cirrhosis of the liver.