DAILY PROFILE OF PLASMA ENDOTHELIN-1 AND ENDOTHELIN-3 IN PRE-ASCITIC CIRRHOSIS - RELATIONSHIPS WITH THE ARTERIAL-PRESSURE AND RENAL-FUNCTION

Background/Aims: Measurements of plasma endothelin-1 and -3 in pre-asc itic cirrhosis have provided controversial results, Similarly, the rol e of the endothelin system in the pathogenesis of volume and hemodynam ic disturbances of cirrhosis is still debated, To provide a further in sight into this issue, we assessed the daily fluctuations of plasma en dothelins and their relationship with arterial pressure and renal func tion in pre-ascitic cirrhosis, Methods: Endothelin-l and -3, plasma re nin activity atrial natriuretic peptide, noradrenaline and mean arteri al 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 sodiu m diet and carrying on their usual activities (supine from 10 pm to 7 am, standing and mobile after 7 am), Glomerular filtration rate and da ily 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-l was higher in patients than in control subject s (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 pati ents with cirrhosis, Norepinephrine and mean arterial pressure did not differ significantly between the two groups, No correlations were fou nd between endothelins and either hemodynamic or neuro-hormonal and re nal function parameters in the two groups, Conclusions: Despite the pr esence of increased effective volemia (as suggested by the reduced pla sma renin activity and elevated atrial natriuretic peptide) and normal adrenergic tone, patients with pre-ascitic cirrhosis show elevated le vels of endothelin-l and endothelin-3 throughout the day, In early cir rhosis circulating endothelins, although elevated, do not appear to pl ay a more prominent role in setting arterial pressure than in normal s ubjects, and endothelin elevation is not detrimental to renal function .