Question: 

Aldosterone is believed to be the main regulator of ENaC activity in the kidney. Its secretion is upregulated by restricting dietary sodium intake. Previously we reported that in animals maintained on a standard diet, ENaC activity was higher in the late distal convoluted tubule/early connecting tubule (DCT2/CNT) than in the late CNT/early collecting duct (CNT/CCD). In contrast, ENaC was upregulated to similar levels on a low salt diet in both segments. This indicates that ENaC activity in the DCT2/CNT is at least in part independent of aldosterone.

Methods: 

To investigate whether aldosterone is necessary for ENaC activity in the DCT2/CNT, we used aldosterone synthase knockout (AS -/-) mice. Whole cell amiloride-sensitive currents (DI_ami) were measured in isolated split open mouse tubules to assess ENaC activity. Experiments were performed in the DCT2/CNT and CNT/CCD obtained either from AS -/- or from wild type (WT) mice, maintained on standard or on low salt diets.

Results: 

In WT animals maintained on a standard diet, DI_ami averaged 60 ± 9 pA in the CNT/CCD. On a low salt diet it was upregulated to 269 ± 81 pA (p < 0.02). DI_ami in the CNT/CCD from AS -/- mice maintained on a standard diet was significantly (p < 0.01) lower then in WT animals: it averaged 22 ± 8 pA and was not stimulated by a low salt diet (21 ± 10 pA). In contrast, in the DCT2/CNT DI_ami did not differ between AS -/- and WT animals maintained on a standard (308 ± 85 pA in WT vs 284 ± 60 pA in AS -/-) or on a low salt diet (382 ± 48 vs 358 ± 59 pA).

Conclusion: 

High ENaC activity in the early part of ASDN (DCT2/CNT) does not depend on circulating aldosterone. In contrast, in later parts of the ASDN (CNT/CCD) ENaC stimulation by sodium restriction depends on the ability of the animals to upregulate aldosterone.