PLASMA ENDOTHELIN-1 AND ENDOTHELIN-3 IN CIRRHOSIS - RELATIONSHIP WITHSYSTEMIC HEMODYNAMICS, RENAL-FUNCTION AND NEUROHUMORAL SYSTEMS

Background/Aims: The postural change from upright to supine is a physi ological maneuvre which increases central blood volume. This model was used to investigate the effects of changes in effective volemia on pl asma endothelin-1 and -3 concentrations in cirrhosis. Methods: Plasma endothelin concentrations, measured by radio-immunoassay, were determi ned in 20 patients with cirrhosis, 10 of whom had ascites, and nine he althy control subjects, in the upright posture and 30, 60 and 120 min after the assumption of the supine position. Results: In the upright p osture, endothelin-1 was 8.9+/-0.4 pg/ml and endothelin-3 3.7+/-0.6 (m ean+/-SEM) pg/ml in control subjects. Endothelin-1 was increased only in patients with ascites (12.7+/-1.4 pg/ml, p<0.05; patients without a scites: 9.7+/-0.7 pg/ml), while endothelin-3 was elevated in both pati ents with and without ascites (8.0+/-1.5 pg/ml, p<0.01; 5.9+/-0.5 pg/m l, p=0.01, respectively). In the supine position, no significant chang es in endothelin-1 or -3 occurred either in patients with ascites or i n controls throughout the observation period, while a reduction in end othelin-3 was found in compensated patients after 30 and 60 min. In pa tients, we found negative correlations between endothelin-3, but not e ndothelin-1, and mean arterial pressure, both in upright (r=-0.59; p<0 .01) and supine (r=-0.56; p=0.01) positions, atrial natriuretic factor (r=0.50; p<0.05) and plasma renin activity (r=0.67; p=0.001) in the s upine position alone. In patients with ascites, endothelin-1 was inver sely correlated with both glomerular filtration rate (upright: r=-0.62 ; p=0.06; supine: r -0.71, p<0.05) and renal sodium excretion (upright : r=-0.82; p<0.01; supine: r=-0.88; p<0.001). Conclusions: Plasma endo thelin-1 and -3 were increased in cirrhosis with ascites, while, in pr e-ascitic cirrhosis, only endothelin-3 was increased in the upright po sture. Although increased endothelin-3 was associated with features su ggesting a reduced effective volemia, it is likely that other mechanis ms than hypovolemia were mainly responsible for high plasma endothelin levels. Increased endothelin production may play a role in circulator y and renal function abnormalities of advanced cirrhosis.