AJP - Regulatory, Integrative and Comparative Physiology, Vol 260, Issue 6 1218-R1228, Copyright © 1991 by American Physiological Society
Inhibition of ANP clearance receptors and endopeptidase 24.11 in maturing rats
R. L. Chevalier, M. Garmey, R. M. Scarborough, J. Linden, R. A. Gomez, M. J. Peach and R. M. Carey
Department of Pediatrics, University of Virginia, Charlottesville 22908.
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.
