Daily profile of plasma endothelin-1 and -3 in pre-ascitic cirrhosis: relationships with the arterial pressure and renal function

Abstract

Background/aims: Measurements of plasma endothelin-1 and -3 in pre-ascitic cirrhosis have provided controversial results. Similarly, the role of the endothelin system in the pathogenesis of volume and hemodynamic disturbances of cirrhosis is still debated. To provide a further insight into this issue, we assessed the daily fluctuations of plasma endothelins and their relationship with arterial pressure and renal function in pre-ascitic cirrhosis.

Methods: Endothelin-1 and -3, plasma renin activity, atrial natriuretic peptide, noradrenaline and mean arterial pressure were measured at 11 pm, 7 am, 9 am and 6 pm in 10 patients with pre-ascitic cirrhosis and in 10 healthy subjects on normal sodium diet and carrying on their usual activities (supine from 10 pm to 7 am, standing and mobile after 7 am). Glomerular filtration rate and daily renal sodium excretion were assessed during the supine period, and from 7 am to 12 am and from 12 am to 10 pm during the standing period.

Results: Endothelin-1 was higher in patients than in control subjects (p=0.000) and did not change during the study. Endothelin-3 was also higher in patients (p=0.002) and showed slight fluctuation in control subjects. The mean daily level of plasma renin activity was lower (p=0.016) and that of atrial natriuretic peptide higher (p=0.000) in patients with cirrhosis. Norepinephrine and mean arterial pressure did not differ significantly between the two groups. No correlations were found between endothelins and either hemodynamic or neuro-hormonal and renal function parameters in the two groups.

Conclusions: Despite the presence of increased effective volemia (as suggested by the reduced plasma renin activity and elevated atrial natriuretic peptide) and normal adrenergic tone, patients with pre-ascitic cirrhosis show elevated levels of endothelin-1 and endothelin-3 throughout the day. In early cirrhosis circulating endothelins, although elevated, do not appear to play a more prominent role in setting arterial pressure than in normal subjects, and endothelin elevation is not detrimental to renal function.