Dietary NaCl modulates Na⁺-H⁺ antiporter activity in renal cortical apical membrane vesicles

An apical membrane Na⁺-H⁺ antiporter mediates proximal tubule NaCl and NaHCO₃ reabsorption. The present studies examined whether chronic changes in dietary NaCl intake lead to an adaptation of the Na⁺-H⁺ antiporter. Rats were maintained either on a low-salt (LS, 0% NaCl) or a high-salt (HS, 2% NaCl) diet for 4 days. Na⁺-H⁺ antiporter was assayed using the acridine orange fluorescence method in apical membrane vesicles prepared by Mg²⁺ aggregation. Rats on LS diet exhibited a higher maximal activity (V(max)) for antiporter activity (0.109 ± 0.008 s^-1) compared with rats on HS diet (0.090 ± 0.008 s^-1; P < 0.01), whereas Na activity (K(Na)) was similar (13.1 ± 1.5 and 14.2 ± 0.8 mM in HS and LS groups, respectively). The modulation of Na⁺-H⁺ antiporter activity was amiloride sensitive. Proton permeability, Na⁺-dependent [³H]glucose uptake, and vesicle enrichments were similar in both groups. In addition, the dietary protocols were not associated with any systemic acid-base disturbances, K⁺ deficiency, or hyperfiltration, conditions that have previously been demonstrated to alter Na⁺-H⁺ antiporter activity. Acute differences in extracellular fluid volume, induced by 10% body weight isohydric expansion failed to affect Na⁺-H⁺ antiporter activity. Thus chronic alterations in dietary NaCl intake alter the maximal activity (V(max)) of the Na⁺-H⁺ antiporter. This adaptation may contribute to decreased NaCl reabsorption in extracellular fluid volume expansion, enhanced NaCl reabsorption in extracellular fluid volume depletion, and enhanced NaHCO₃ reabsorption in chronic metabolic alkalosis associated with volume contraction.