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 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.
Suzuki
E
E
Second Department of Internal Medicine, Faculty of Medicine, University of Tokyo, Japan.
Hirata
Y
Y
Matsuoka
H
H
Sugimoto
T
T
Hayakawa
H
H
Sugimoto
T
T
Kangawa
K
K
Minamino
N
N
Matsuo
H
H
D000704:Analysis of Variance; D000818:Animals; D009320:Atrial Natriuretic Factor / Q000097:blood / Q000302:isolation & purification / Q000652:urine*; D001794:Blood Pressure / Q000187:drug effects; D002850:Chromatography, Gel; D002851:Chromatography, High Pressure Liquid; D007189:Indans / Q000494:pharmacology*; D009318:Natriuresis / Q000187:drug effects; D015260:Neprilysin / Q000037:antagonists & inhibitors*; D011422:Propionates / Q000494:pharmacology*; D011863:Radioimmunoassay; D051381:Rats; D011919:Rats, Inbred Strains; D012982:Sodium, Dietary
D007189:Indans; D011422:Propionates; D012982:Sodium, Dietary; D009320:Atrial Natriuretic Factor; C062766:candoxatril; D015260:Neprilysin