Long-term regulation of renal Na-dependent cotransporters and ENaC: response to altered acid-base intake

Increased systemic acid intake is associated with an increase in apical Na/ H exchange in the renal proximal tubule mediated by the type 3 Na/H exchang er (NHE3). Because NHE3 mediates both proton secretion and Na absorption, i ncreased NHE3 activity could inappropriately perturb Na balance unless ther e are compensatory changes in Na handling. In this study, we use semiquanti tative immunoblotting of rat kidneys to investigate whether acid loading is associated with compensatory decreases in the abundance of renal tubule Na transporters other than NHE3. Long-term (i.e., 7-day) acid loading with NH 4Cl produced large decreases in the abundances of the thiazide-sensitive Na -Cl cotransporter (TSC/NCC) of the distal convoluted tubule and both the be ta- and gamma-subunits of the amiloride-sensitive epithelial Na channel (EN aC) of the collecting duct. In addition, the renal cortical abundance of th e proximal type 2 Na-dependent phosphate transporter (NaPi-2) was markedly decreased. In contrast, abundances of the bumetanide-sensitive Na-K-2Cl cot ransporter of the thick ascending limb and the alpha-subunit of ENaC were u nchanged. A similar profile of changes was seen with short-term (16-h) acid loading. Longterm (7-day) base loading with NaHCO3 resulted in the opposit e pattern of response with marked increases in the abundances of the beta- and gamma-subunits of ENaC and NaPi-2. These adaptations may play critical roles in the maintenance in Na balance when changes in acid-base balance oc cur.