CHARACTERIZATION OF ATRIAL-NATRIURETIC-PEPTIDE IN URINE FROM RATS TREATED WITH A NEUTRAL ENDOPEPTIDASE INHIBITOR

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<0.05) was associated with a marked increase in the urinary ANP excretion (+1200%, p<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 2.5K. Further analysis by reverse phase high performance liquid chromatography showed that ir-ANP in the plasma of Dahl S rats was α-rANP (1-28), while that in the urine from rats treated with candoxatril was α-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. © 1992.