1. Sodium retention in cirrhosis may be partly attributable to resistance to a putative circulating natriuretic factor. In cirrhosis, plasma concentrations of atrial natriuretic peptide are often increased in the presence of sodium retention.
2. In order to determine whether the kidney of cirrhotic animals may be insensitive to atrial natriuretic peptide, isolated perfused kidneys from six cirrhotic and five control rats were exposed to increasing concentrations of atrial natriuretic peptide. Cirrhosis had been induced by carbon tetrachloride administration.
3. Excretion in vivo of a 2 mmol sodium load, administered by gavage, was impaired in cirrhotic animals for up to 4 h as compared with control animals (4.2 ± 1.9 vs34.9± 13.4% P < 0.05).
4. During perfusion at 110 mmHg in the absence of atrial natriuretic peptide, sodium excretion by isolated kidneys of cirrhotic animals tended to be lower than in control animals, but the difference was not significant (4.93 ± 1.01 vs 8.41 ± 1.48 μmol min−1 g−1 kidney weight, P = 0.09). There was a smaller increase in urinary sodium excretion by the kidneys of cirrhotic rats compared with control rats in the presence of atrial natriuretic peptide at 10, 50 and 200 pmol/l (respectively: 0.06 ± 0.08 vs 1.29 ± 0.35 μmol min−1 g−1 kidney weight, P < 0.02; 0.49 ± 0.08 vs 1.82 ± 0.42 μmol min−1 g−1 kidney weight, P < 0.03; 1.42 ± 0.16 vs 3.23 ± 0.73 μmol min−1 g−1 kidney weight, P < 0.05), but not at 1000 pmol/l.
5. In this animal model of cirrhosis, renal resistance to the natriuretic action of atrial natriuretic peptide at physiological and pathophysiological concentrations may contribute to sodium retention.