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

• Published in: American journal of physiology. Renal physiology 2007-10, Vol.293 (4), p.F1314-F1324
• Main Authors: Kim, Young Hee, Pech, Vladimir, Spencer, Kathryn B, Beierwaltes, William H, Everett, Lorraine A, Green, Eric D, Shin, Wonkyong, Verlander, Jill W, Sutliff, Roy L, Wall, Susan M
• Format: Article
• Language: English
• Subjects: Adrenal Glands - physiology; Aldosterone - blood; Aldosterone - pharmacology; Amiloride - pharmacology; Animals; Anion Transport Proteins - genetics; Anion Transport Proteins - metabolism; Blood pressure; Blood Pressure - physiology; Cells; Colon - metabolism; Epithelial Sodium Channels - drug effects; Epithelial Sodium Channels - genetics; Epithelial Sodium Channels - metabolism; Female; Hormones; Hypothalamus - physiology; Kidney - metabolism; Kidneys; Male; Mice; Mice, Knockout; Proteins; Rodents; Sodium - metabolism; Sodium Channel Blockers - pharmacology; Sodium Chloride Symporters - metabolism; Thyroid Gland - metabolism
• ISSN: 1931-857X; 1522-1466
• DOI: 10.1152/ajprenal.00155.2007

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.