High Salt Intake-Induced Changes in Atrial Natriuretic Factor Kinetics Are Mediated by Clearance Receptors

Abstract

We have reported a paradoxical plasma atrial natriuretic factor (ANF) decline following prolonged high salt intake that was attributed to an increased tissue uptake of circulating ANF, leading to its augmented distribution volume (V_ss) and metabolic clearance rate (MCR) as compared with control rats on a standard diet. To explore this phenomenon further, we evaluated possible chronic salt-loading-induced changes in ANF clearance (C-ANF) receptors, which appear to play a major role in ANF removal from the circulation. We studied changes in plasma [¹²⁵I]ANF(1–28) and its pharmacokinetics after preoccupation of C-ANF receptors by its specific ligand, C-ANF(4–23), in high-salt-treated rats and their controls. Following C-ANF(4–23) administration, we detected significantly higher circulating [¹²⁵I]ANF levels throughout the study period (8 min) in high-salt-fed rats compared with the controls (280–470% vs 100–215% increase of basal values, P < 0.05). C-ANF(4–23) infusion caused a significantly greater decrease of the metabolic clearance rate and distribution volume of [¹²⁵I]ANF in high-salt-fed rats than in control animals (74 ± 6% vs 41 ± 6% and 75 ± 4% vs 50 ± 5% of basal values, respectively; P < 0.05). These data suggest that a prolonged high salt diet may increase the availability of C-ANF receptors and, through this mechanism, may negatively modulate plasma ANF concentrations. C-ANF receptors may thus fulfill a regulatory function on circulating ANF during prolonged salt loading in rats.