Rat proximal NHE3 adapts to chronic acid-base disorders but not to chronic changes in dietary NaCl intake

Abstract

In the proximal tubule, the apical Na+/H+ exchanger identified as NHE3 mediates most NaCl and NaHCO3 absorption. The purpose of this study was to analyze the long-term regulation of NHE3 during alkalosis induced by dietary NaHCO3 loading and changes in NaCl intake. Sprague-Dawley rats exposed to a low-NaCl, high-NaCl, or NaHCO3 diet for 6 days were studied. Renal cortical apical membrane vesicles (AMV) were prepared from treated and normal rats. Na+/H+ exchange was assayed as the initial rate of 22Na+ uptake in the presence of an outward H+ gradient. 22Na+uptake measured in the presence of high-dose 5-( N-ethyl- N-isopropyl) amiloride was not different among models. Changes in NaCl intake did not affect NHE3 activity, whereas NaHCO3 loading inhibited22Na+ uptake by 30%. AMV NHE3 protein abundance assessed by Western blot analysis was unaffected during changes in NaCl intake. During NaHCO3 loading, NHE3 protein abundance was decreased by 65%. We conclude that proximal NHE3 adapts to chronic metabolic acid-base disorders but not to changes in dietary NaCl intake.