ENaC is active in the ASDN in the absence of mineralocorticoid

Aldosterone controls extracellular volume and blood pressure by regulating Na + reabsorption via ENaC across epithelial cells of the aldosterone‐sensitive distal nephron (ASDN). Our recent findings suggest that complementary systems function in parallel with aldosterone to modulate ENaC activity, including AVP and purinergic signaling localized to the distal nephron. To explore further the relation of aldosterone with this other regulation and to test the primacy of aldosterone in regulation of ENaC activity, we used mice with bilateral adrenalectomy . The activity of ENaC in the murine ASDN was assayed with patch‐clamp electrophysiology in freshly isolated split‐open tubules. In normal mice, ENaC activity is inversely related to Na + intake. This relation is thought to be a manifestation, at least in part, of changes in aldosterone levels. Consistent with this, treatment with the mineralocorticoid DOCA reversed the effects of a high Na + diet returning ENaC activity to normal levels. Unexpectedly, ENaC in the ASDN of Adx mice had robust activity despite the absence of adrenal corticosteroids, as measured with HPLC. Moreover, the response to high salt consumption was similar in both Adx and wild type mice with respect to the number of active channels. Intriguingly, ENaC is more active in Adx mice compared to wild type mice at all dietary Na + regimens tested. ENaC activity in Adx mice is likely controlled primarily by AVP and/or Ang II responding mostly to changes in plasma tonicity and to a lesser degree volume status. These results demonstrate that in complement to corticosteroids, other hormones play an important role in setting ENaC activity and that ENaC can be present and functional in the ASDN even in the absence of adrenal corticosteroids.