Collecting duct-specific endothelin b receptor knockout increases enac activity

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

Research output: Contribution to journalArticlepeer-review

52 Scopus citations


Collecting duct (CD)-derived endothelin-1 (ET-1) acting via endothelin B (ETB) receptors promotes Na + excretion. Compromise of ET-1 signaling or ETB receptors in the CD cause sodium retention and increase blood pressure. Activity of the epithelial Na + channel (ENaC) is limiting for Na + reabsorption in the CD. To test for ETB receptor regulation of ENaC, we combined patch-clamp electrophysiology with CD-specific knockout (KO) of endothelin receptors. We also tested how ET-1 signaling via specific endothelin receptors influences ENaC activity under differing dietary Na + regimens. ET-1 significantly decreased ENaC open probability in CD isolated from wild-type (WT) and CD ETA KO mice but not CD ETB KO and CD ETA/B KO mice. ENaC activity in WT and CD ETA but not CD ETB and CD ETA/B KO mice was inversely related to dietary Na + intake. ENaC activity in CD ETB and CD ETA/B KO mice tended to be elevated under all dietary Na + regimens compared with WT and CD ETA KO mice, reaching significance with high (2%) Na + feeding. These results show that the bulk of ET-1 inhibition of ENaC activity is mediated by the ETB receptor. In addition, they could explain the Na + retention and elevated blood pressure observed in CD ET-1 KO, CD ETB KO, and CD ETA/B KO mice consistent with ENaC regulation by ET-1 via ETB receptors contributing to the antihypertensive and natriuretic effects of the local endothelin system in the mammalian CD.

Original languageEnglish (US)
Pages (from-to)C188-C194
JournalAmerican Journal of Physiology - Cell Physiology
Issue number1
StatePublished - Jan 2012
Externally publishedYes


  • Endothelin-1
  • Hypertension
  • Sodium transport

ASJC Scopus subject areas

  • Physiology
  • Cell Biology


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