Collecting duct-specific endothelin B receptor knockout increases ENaC activity

Am J Physiol Cell Physiol. 2012 Jan 1;302(1):C188-94. doi: 10.1152/ajpcell.00301.2011. Epub 2011 Sep 14.


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.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural

MeSH terms

  • Amiloride / pharmacology
  • Animals
  • Endothelin-1 / metabolism
  • Endothelin-1 / physiology
  • Epithelial Sodium Channel Blockers
  • Epithelial Sodium Channels / metabolism*
  • Female
  • Hypertension / genetics
  • Hypertension / metabolism
  • Kidney Tubules, Collecting / metabolism*
  • Male
  • Mice
  • Mice, Knockout
  • Natriuresis / genetics
  • Receptor, Endothelin B / deficiency*
  • Receptor, Endothelin B / genetics*
  • Sodium / metabolism
  • Up-Regulation / genetics*


  • Endothelin-1
  • Epithelial Sodium Channel Blockers
  • Epithelial Sodium Channels
  • Receptor, Endothelin B
  • Amiloride
  • Sodium