Long-term regulation of ENaC expression in kidney by angiotensin II

Kathleen T. Beutler, Shyama Masilamani, Sharon Turban, Jakob Nielsen, Heddwen L. Brooks, Shana Ageloff, Robert A. Fenton, Randall K. Packer, Mark A. Knepper

Research output: Contribution to journalArticlepeer-review

146 Scopus citations


We carried out semiquantitative immunoblotting of kidney to identify apical sodium transporter proteins whose abundances are regulated by angiotensin II. In NaCl-restricted rats (0.5 mEq Na/200 g BW/d), the type 1 angiotensin II receptor (AT1 receptor) antagonist, candesartan, (1 mg/kg of body weight per day SC for 2 days) markedly decreased the abundance of the α subunit of the epithelial sodium channel (ENaC). This subunit has been shown to be rate-limiting for assembly of mature ENaC complexes. In addition, systemic infusion of angiotensin II increased αENaC protein abundance in rat kidney cortex. The decrease in αENaC protein abundance in response to AT1 receptor blockade was associated with a fall in αENaC mRNA abundance (real-time RT-PCR), consistent with transcriptionally mediated regulation. The effect of AT1 receptor blockade on αENaC expression was not blocked by spironolactone, suggesting a direct role of the AT1 receptor in regulation of αENaC gene expression. Candesartan administration was also found to increase the abundances of the β and γ subunits. The increase in β and γENaC protein abundance was not associated with a significant increase in the renal abundances of the corresponding mRNAs, suggesting a posttranscriptional mechanism. Immunocytochemistry confirmed the increase in β and γENaC protein abundance and demonstrated candesartan-induced ENaC internalization in collecting duct cells. The results support the view that the angiotensin II receptor regulates ENaC abundance, consistent with a role for angiotensin II in regulation of collecting duct function.

Original languageEnglish (US)
Pages (from-to)1143-1150
Number of pages8
Issue number5
StatePublished - May 1 2003


  • Aldosterone
  • Angiotensin antagonist
  • Receptors, angiotensin II
  • Sodium channels

ASJC Scopus subject areas

  • Internal Medicine


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