Renal response to atrial natriuretic peptide in patients with advanced liver cirrhosis

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Abstract

Sodium retention in liver cirrhosis is thought to be due to, among other things, lack of a natriuretic factor or failure to respond to one. α-Human-atrial natriuretic peptide is a peptide that accounts partly or entirely for the circulating natriuretic activity in man.

In the present study, we have evaluated the effects of the bolus administration of synthetic α-human-atrial natriuretic peptide (1 μg per kg) to patients with liver cirrhosis and variable degrees of sodium retention, α-Human-atrial natriuretic peptide induced rapid and marked increases of diuresis and natriuresis in patients without sodium retention or with moderate retention. The results were comparable to those obtained in six healthy control subjects. Conversely, the diuretic and natriuretic effects of α-human-atrial natriuretic peptide were attenuated or completely blunted in patients with avid sodium retention. The two groups of patients differed not only in basal sodium excretion, but also in plasma renin activity and in plasma aldosterone levels, suggesting that the reduced responsiveness to atrial natriuretic peptide might be due to excessive antagonism by antinatriuretic factors. The direct relationship between baseline sodium excretion rate and that stimulated by human-atrial natriuretic peptide administration was consistent with this interpretation. In none of the subjects did plasma renin activity peptide and cortisol levels change after human-atrial natriuretic peptide, while plasma aldosterone slightly declined in cirrhotics. Blood pressure fell after the administration of the peptide, with the drop greater in cirrhotic than in normal subjects. These data show that the hormonal and the vascular effects of human-atrial natriuretic peptide are not blunted in cirrhotics. Since angiotensin II plays a central role in sustaining blood pressure in patients with advanced liver cirrhosis, the marked drop in blood pressure has been tentatively ascribed to the specific ability of atrial natriuretic peptide to antagonize angiotensin, but other mechanisms cannot be excluded.

In conclusion, these data suggest that renal unrespon-siveness to atrial natriuretic peptide develops in patients with liver cirrhosis during the course of the disease and is strictly related to the severity of sodium retention.

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