Renal tubular responsiveness to atrial natriuretic peptide in sodium-retaining chronic caval dogs: A possible role for kinins and luminal actions of the peptide

Louis Legault, Peter Cernacek, Mortimer Levy, Elizabeth Maher, David Farber

Research output: Contribution to journalArticle

18 Scopus citations

Abstract

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 languageEnglish (US)
Pages (from-to)1425-1435
Number of pages11
JournalJournal of Clinical Investigation
Volume90
Issue number4
DOIs
StatePublished - Oct 1992

Keywords

  • Ascites
  • Neutral endopeptidase
  • Sodium excretion
  • cGMP

ASJC Scopus subject areas

  • Medicine(all)

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