Aldosterone-independent regulation of the epithelial Na + channel (ENaC) by vasopressin in adrenalectomized mice

Elena Mironova, Vladislav Bugaj, Karl P. Roos, Donald E. Kohan, James D. Stockand

Research output: Contribution to journalArticlepeer-review

41 Scopus citations

Abstract

The epithelial Na + channel (ENaC) in the aldosterone-sensitive distal nephron (ASDN) is under negative-feedback regulation by the renin-angiotensin-aldosterone system in protection of sodium balance and blood pressure. We test here whether aldosterone is necessary and sufficient for ENaC expression and activity in the ASDN. Surprisingly, ENaC expression and activity are robust in adrenalectomized (Adx) mice. Exogenous mineralocorticoid increases ENaC activity equally well in control and Adx mice. Plasma [AVP] is significantly elevated in Adx vs. control mice. Vasopressin (AVP) stimulates ENaC. Inhibition of the V 2 AVP receptor represses ENaC activity in Adx mice. The absence of aldosterone combined with elevated AVP release compromises normal feedback regulation of ENaC in Adx mice in response to changes in sodium intake. These results demonstrate that aldosterone is sufficient but not necessary for ENaC activity in the ASDN. Aldosterone- independent stimulation by AVP shifts the role of ENaC in the ASDN from protecting Na + balance to promoting water reabsorption. This stimulation of ENaC likely contributes to the hyponatremia of adrenal insufficiency.

Original languageEnglish (US)
Pages (from-to)10095-10100
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume109
Issue number25
DOIs
StatePublished - Jun 19 2012

Keywords

  • Diabetes insipidus
  • Epithelial transport
  • Hypertension
  • Sodium excretion
  • Sodium wasting

ASJC Scopus subject areas

  • General

Fingerprint Dive into the research topics of 'Aldosterone-independent regulation of the epithelial Na <sup>+</sup> channel (ENaC) by vasopressin in adrenalectomized mice'. Together they form a unique fingerprint.

Cite this