60% of chronic caval dogs with ascites did not respond to atrial natriuretic peptide (ANP) (75 ng · kg-1 · min-1) with a natriuresis (TIVC-NR; ΔUNaV = 2±0.8 μeq/min) whereas the remaining 40% responded normally (TIVC-R; ΔUNaV = 216±50 μeq/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 (ΔUNaV = 67±2 μeq/min) and permitted a natriuresis in the presence of ANP (ΔUNaV = 97±18 μeq/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 UNaV when given to TIVC-R and normal dogs. Providing bradykinin to TIVC-NR now permitted an increment in ΔUNaV (62 μeq/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.
|Original language||English (US)|
|Number of pages||11|
|Journal||Journal of Clinical Investigation|
|Publication status||Published - Oct 1992|
- Neutral endopeptidase
- Sodium excretion
ASJC Scopus subject areas