Renal Tubular Responsiveness to Atrial Natriuretic

60% of chronic caval dogs with ascites did not respond to atrial natriuretic peptide (ANP) (75 ng kg-' * min-') with a natriuresis (TIVC-NR; AUNaV = 2±0.8 ,geq/min) whereas the remaining 40% responded normally (TIVC-R; AUNaV = 216±50 Ateq/min). Since proximal tubule neutral endopeptidase 24:11 (NEP) destroys most of intrarenal luminal ANP and kinins, we attempted to convert TIVC-NR into TIVC-R by providing NEP inhibition with SQ 28603 at 30 mg/kg. This potent and specific NEP inhibitor produced a natriuresis when administered alone to nine TIVC-NR dogs (AUN.V = 67±2 geq/min) and permitted a natriuresis in the presence of ANP (AUNaV = 97±18 leq/min). A natriuretic response to ANP could also be induced in TIVC-NR dogs by providing renal arterial bradykinin or intravenous captopril, a kininase inhibitor. Urodilatin, a natriuretic peptide not destroyed by intrarenal NEP was without effect in TIVC-NR dogs but increased UNV when given to TIVC-R and normal dogs. Providing bradykinin to TIVC-NR now permitted an increment in AUN.V (62 ,eq/min) when urodilatin was reinfused. TIVC-R dogs could be converted into TIVC-NR by pretreating with a specific bradykinin antagonist before infusing ANP. We conclude that TIVC-NR dogs are deficient in intrarenal kinins but are converted to responding dogs after NEP inhibition because of increased kinin delivery to the inner medullary collecting duct. (J. Clin. Invest. 1992. 90:1425-1435.)