Molecular forms and biological activity of atrial natriuretic factor in patients with cirrhosis and ascites

Patients with cirrhosis and ascites show sodium retention and normal or increased plasma levels of atrial natriuretic factor, a peptide with powerful natriuretic activity. To investigate whether this paradoxical observation could be related to a dysregulation in the process of synthesis and maturation of atrial natriuretic factor leading to abnormal molecular forms lacking biological activity, the chromatographic patterns of atrial natriuretic factor contained in plasma extracts from 10 patients with cirrhosis and ascites and 6 healthy subjects were compared. Atrial natriuretic factor from cirrhotic patients was also tested in two different radioreceptor assays, which detect the biologically active form(s) of this peptide. Patients with cirrhosis and ascites had higher plasma levels of atrial natriuretic factor (81.3 +/- 8.5 pg/ml, p less than 0.001) than control subjects (29.8 +/- 3.2 pg/ml). High-performance liquid chromatography analysis of atrial natriuretic factor showed an identical chromatographic pattern in cirrhotic patients and control subjects. Three peaks related to the atrial natriuretic factor prohormone were observed in cirrhotic patients and control subjects, accounting for 64%, 23% and 11% of the total atrial natriuretic factor in cirrhotic patients and 63%, 18% and 8% of the total atrial natriuretic factor in control subjects. The main peak eluted at the same position of synthetic human atrial natriuretic factor (Ser 99-Tyr 126), which represents the major active form of the circulating hormone. Cirrhotic atrial natriuretic factor displayed the same ability to inhibit the binding of 125I-atrial natriuretic factor to rat glomerular and bovine adrenal membrane receptors as synthetic human atrial natriuretic factor.(ABSTRACT TRUNCATED AT 250 WORDS)