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  • Title: Characterization of atrial natriuretic peptide in urine from rats treated with a neutral endopeptidase inhibitor.
    Author: Suzuki E, Hirata Y, Matsuoka H, Sugimoto T, Hayakawa H, Sugimoto T, Kangawa K, Minamino N, Matsuo H.
    Journal: Biochem Biophys Res Commun; 1992 Feb 14; 182(3):1270-6. PubMed ID: 1531753.
    Abstract:
    To explore the mechanisms for the natriuretic effects of a neutral endopeptidase inhibitor, candoxatril, the concentration of atrial natriuretic peptide (ANP) and its molecular forms in the urine of Dahl salt-sensitive (S) rats were examined. Candoxatril-induced natriuresis (+120%, p less than 0.05) was associated with a marked increase in the urinary ANP excretion (+1200%, p less than 0.05). Analysis by Sephadex G-50 gel filtration revealed that molecular weight of the major fraction of immunoreactive (ir-) ANP in the plasma of candoxatril-treated Dahl S rats was 3K, whereas that in the urine was 2.5 K. Further analysis by reverse phase high performance liquid chromatography showed that ir-ANP in the plasma of Dahl S rats was alpha-rANP (1-28), while that in the urine from rats treated with candoxatril was alpha-rANP (1-25). These results indicate that candoxatril inhibits the complete degradation of ANP in the kidney, thereby increasing the amount of biologically active ANP reaching the distal nephron and contributing to natriuresis.
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