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

Authors

  • Wladimiro Jiménez PhD.,

    Corresponding author
    1. Hormonal Laboratory and Liver Unit, Hospital Clínic i Provincial, University of Barcelona, Barcelona 08036, Spain
    2. Clinical Research Institute of Montreal, Montreal, Quebec, Canada H2W 1R7
    • Hormonal Laboratory, Hospital Clinic i Provincial, Villarroel 170, Barcelona 08036, Spain
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  • Jolanta Gutkowska,

    1. Hormonal Laboratory and Liver Unit, Hospital Clínic i Provincial, University of Barcelona, Barcelona 08036, Spain
    2. Clinical Research Institute of Montreal, Montreal, Quebec, Canada H2W 1R7
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  • Pere Ginés,

    1. Hormonal Laboratory and Liver Unit, Hospital Clínic i Provincial, University of Barcelona, Barcelona 08036, Spain
    2. Clinical Research Institute of Montreal, Montreal, Quebec, Canada H2W 1R7
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  • Vicente Arroyo,

    1. Hormonal Laboratory and Liver Unit, Hospital Clínic i Provincial, University of Barcelona, Barcelona 08036, Spain
    2. Clinical Research Institute of Montreal, Montreal, Quebec, Canada H2W 1R7
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  • Francisca Rivera,

    1. Hormonal Laboratory and Liver Unit, Hospital Clínic i Provincial, University of Barcelona, Barcelona 08036, Spain
    2. Clinical Research Institute of Montreal, Montreal, Quebec, Canada H2W 1R7
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  • Joan Rodés

    1. Hormonal Laboratory and Liver Unit, Hospital Clínic i Provincial, University of Barcelona, Barcelona 08036, Spain
    2. Clinical Research Institute of Montreal, Montreal, Quebec, Canada H2W 1R7
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Abstract

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 < 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. In conclusion this study demonstrates that atrial natriuretic factor of patients with cirrhosis and ascites has an equipotent binding activity to its receptor as to that of synthetic human atrial natriuretic factor and possesses the same molecular weight and biologically active forms as atrial natriuretic factor of normal subjects. These data indicate that in cirrhosis there is no dysregulation in the atrial natriuretic factor maturation process. (HEPATOLOGY 1991;14:601–607.)

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