Reduced ENaC protein abundance contributes to the lower blood pressure observed in pendrin-null mice

Am J Physiol Renal Physiol. 2007 Oct;293(4):F1314-24. doi: 10.1152/ajprenal.00155.2007. Epub 2007 Aug 8.


Pendrin (encoded by Pds, Slc26a4) is a Cl(-)/HCO(3)(-) exchanger expressed in the apical regions of type B and non-A, non-B intercalated cells of kidney and mediates renal Cl(-) absorption, particularly when upregulated. Aldosterone increases blood pressure by increasing absorption of both Na(+) and Cl(-) through increased protein abundance and function of Na(+) transporters, such as the epithelial Na(+) channel (ENaC) and the Na(+)-Cl(-) cotransporter (NCC), as well as Cl(-) transporters, such as pendrin. Because aldosterone analogs do not increase blood pressure in Slc26a4(-/-) mice, we asked whether Na(+) excretion and Na(+) transporter protein abundance are altered in kidneys from these mutant mice. Thus wild-type and Slc26a4-null mice were given a NaCl-replete, a NaCl-restricted, or NaCl-replete diet and aldosterone or aldosterone analogs. Abundance of the major renal Na(+) transporters was examined with immunoblots and immunohistochemistry. Slc26a4-null mice showed an impaired ability to conserve Na(+) during dietary NaCl restriction. Under treatment conditions in which circulating aldosterone is increased, alpha-, beta-, and 85-kDa gamma-ENaC subunit protein abundances were reduced 15-35%, whereas abundance of the 70-kDa fragment of gamma-ENaC was reduced approximately 70% in Slc26a4-null relative to wild-type mice. Moreover, ENaC-dependent changes in transepithelial voltage were much lower in cortical collecting ducts from Slc26a4-null than from wild-type mice. Thus, in kidney, ENaC protein abundance and function are modulated by pendrin or through a pendrin-dependent downstream event. The reduced ENaC protein abundance and function observed in Slc26a4-null mice contribute to their lower blood pressure and reduced ability to conserve Na(+) during NaCl restriction.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adrenal Glands / physiology
  • Aldosterone / blood
  • Aldosterone / pharmacology
  • Amiloride / pharmacology
  • Animals
  • Anion Transport Proteins / genetics
  • Anion Transport Proteins / metabolism*
  • Blood Pressure / physiology*
  • Colon / metabolism
  • Epithelial Sodium Channels / drug effects
  • Epithelial Sodium Channels / genetics
  • Epithelial Sodium Channels / metabolism*
  • Female
  • Hypothalamus / physiology
  • Kidney / metabolism*
  • Male
  • Mice
  • Mice, Knockout
  • Sodium / metabolism
  • Sodium Channel Blockers / pharmacology
  • Sodium Chloride Symporters / metabolism
  • Sulfate Transporters
  • Thyroid Gland / metabolism


  • Anion Transport Proteins
  • Epithelial Sodium Channels
  • Slc26a4 protein, mouse
  • Sodium Channel Blockers
  • Sodium Chloride Symporters
  • Sulfate Transporters
  • Aldosterone
  • Amiloride
  • Sodium