title: Renal tubular responsiveness to atrial natriuretic peptide in sodium-retaining chronic caval dogs. A possible role for kinins and luminal actions of the peptide.
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; delta UNaV = 2 +/- 0.8 mu eq/min) whereas the remaining 40% responded normally (TIVC-R; delta UNaV = 216 +/- 50 mu eq/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 (delta UNaV = 67 +/- 2 mu eq/min) and permitted a natriuresis in the presence of ANP (delta UNaV = 97 +/- 18 mu eq/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 delta UNaV (62 mu 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.
authors.affiliation: Department of Physiology, McGill University, Montreal, Quebec, Canada.
authors.forename: L
authors.initials: L
authors.lastname: Legault
authors.forename: P
authors.initials: P
authors.lastname: Cernacek
authors.forename: M
authors.initials: M
authors.lastname: Levy
authors.forename: E
authors.initials: E
authors.lastname: Maher
authors.forename: D
authors.initials: D
authors.lastname: Farber
mesh_terms: D000409:Alanine / Q000031:analogs & derivatives*; D000818:Animals; D001201:Ascites / Q000378:metabolism; D009320:Atrial Natriuretic Factor / Q000378:metabolism / Q000494:pharmacology*; D002908:Chronic Disease; D006152:Cyclic GMP / Q000031:analogs & derivatives / Q000494:pharmacology; D004285:Dogs; D005260:Female; D007684:Kidney Tubules / Q000187:drug effects* / Q000378:metabolism; D007705:Kinins / Q000502:physiology*; D008297:Male; D015260:Neprilysin / Q000037:antagonists & inhibitors / Q000494:pharmacology; D011480:Protease Inhibitors / Q000494:pharmacology; D018002:Receptors, Bradykinin; D017981:Receptors, Neurotransmitter / Q000187:drug effects; D012964:Sodium / Q000378:metabolism*
chemical_list: D007705:Kinins; D011480:Protease Inhibitors; D018002:Receptors, Bradykinin; D017981:Receptors, Neurotransmitter; C065359:SQ 28603; C016276:8-bromocyclic GMP; D009320:Atrial Natriuretic Factor; D012964:Sodium; D015260:Neprilysin; D006152:Cyclic GMP; D000409:Alanine