title: Inhibition of ANP clearance receptors and endopeptidase 24.11 in maturing rats.
abstract: Systemic clearance of atrial natriuretic peptide (ANP) decreases during postnatal development. To determine the relative contribution of ANP clearance (C) receptors and neutral endopeptidase 24.11 (NEP; EC 3.4.24.11) in regulation of plasma ANP concentration ([ANP]) during maturation, 18- to 60-day-old male Sprague-Dawley rats were anesthetized and infused with rat ANP (35 ng.kg-1.min-1). Infusion of the NEP inhibitor phosphoramidon increased [ANP] and urine guanosine 3',5'-cyclic monophosphate (cGMP) excretion in both weanling and adult rats. Infusion of C-ANP, an analogue that binds C receptors selectively, resulted in a greater rise in [ANP] in preweaned than in adult rats, suggesting a maturational decrease in function of C receptors. Despite the increase in [ANP], however, urine flow, cGMP, and sodium excretion failed to increase in preweaned compared with adult rats. Combined infusion of phosphoramidon and C-ANP resulted in a marked increase in [ANP] and cGMP excretion in weanling and adult rats. These results indicate that both C receptors and NEP modulate plasma [ANP] in the physiological range and that each pathway compensates when the other is inhibited. Age-related differences in the renal response to ANP clearance inhibitors may have important physiological implications in the regulation of sodium balance during development.
authors.affiliation: Department of Pediatrics, University of Virginia, Charlottesville 22908.
authors.forename: R L
authors.initials: RL
authors.lastname: Chevalier
authors.forename: M
authors.initials: M
authors.lastname: Garmey
authors.forename: R M
authors.initials: RM
authors.lastname: Scarborough
authors.forename: J
authors.initials: J
authors.lastname: Linden
authors.forename: R A
authors.initials: RA
authors.lastname: Gomez
authors.forename: M J
authors.initials: MJ
authors.lastname: Peach
authors.forename: R M
authors.initials: RM
authors.lastname: Carey
mesh_terms: D000818:Animals; D009320:Atrial Natriuretic Factor / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics / Q000494:pharmacology / Q000652:urine; D006152:Cyclic GMP / Q000652:urine; D006020:Glycopeptides / Q000008:administration & dosage / Q000494:pharmacology; D007262:Infusions, Intravenous; D008297:Male; D008657:Metabolic Clearance Rate / Q000187:drug effects; D015260:Neprilysin / Q000037:antagonists & inhibitors* / Q000502:physiology; D010446:Peptide Fragments / Q000008:administration & dosage / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D017461:Receptors, Atrial Natriuretic Factor; D011956:Receptors, Cell Surface / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D013820:Thermolysin / Q000037:antagonists & inhibitors
chemical_list: D006020:Glycopeptides; D010446:Peptide Fragments; D011956:Receptors, Cell Surface; C065367:atrial natriuretic factor (4-23)NH2, de-Gln(18)-de-Ser(19)-de-Gly(20,22)-de-Leu(21)-; D009320:Atrial Natriuretic Factor; D015260:Neprilysin; D013820:Thermolysin; D017461:Receptors, Atrial Natriuretic Factor; D006152:Cyclic GMP; C008890:phosphoramidon