The renal physiology of pendrin (SLC26A4) and its role in hypertension.
SLC26A4 (pendrin, PDS) is a Na+-independent, Cl-/HCO3-/OH- exchanger that is expressed in the apical regions of type B and non-A, non-B intercalated cells within the cortical collecting duct (CCD), the connecting tubule and the distal convoluted tubule where it mediates HCO3- secretion and Cl- absorption. SLC26A4 is upregulated with aldosterone analogues and with Cl- restriction. While under basal conditions no renal abnormalities are observed in mice and humans with genetic disruption of SLC26A4 (Pendred syndrome), differences become apparent under conditions wherein the transporter is stimulated. Following treatment with aldosterone analogues, e.g. deoxycorticosterone pivalate (DOCP), weight gain and hypertension are observed in Slc26a4+/+ but not in Slc26a4-/- mice. During dietary NaCl restriction, a model in which serum aldosterone is appropriately increased, urinary volume and urinary excretion of Cl- are greater in Slc26a4-/- than in wild-type mice which results in apparent vascular volume contraction in Slc26a4-/- mice. Moreover, during NaCl restriction or following DOCP treatment, Slc26a4-/- mice have a higher serum HCO3- than wild type mice from an impaired ability to excrete OH- equivalents. In conclusion, SLC26A4 regulates blood pressure and arterial pH, likely by participating in the renal regulation of net acid and Cl- excretion.
Wall
Susan M
SM
Renal Division, Emory University School of Medicine, 1639 Pierce Drive, NE Atlanta, GA 30322, USA.
D000042:Absorption / Q000187:drug effects; D000136:Acid-Base Equilibrium / Q000187:drug effects; D000450:Aldosterone / Q000031:analogs & derivatives; D000818:Animals; D027321:Anion Transport Proteins / Q000378:metabolism*; D001639:Bicarbonates / Q000378:metabolism; D001794:Blood Pressure / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D002712:Chlorides / Q000378:metabolism; D003001:Cloning, Molecular; D006973:Hypertension / Q000378:metabolism* / Q000503:physiopathology; D007668:Kidney / Q000502:physiology*; D051379:Mice; D012965:Sodium Chloride / Q000494:pharmacology; D000076988:Sulfate Transporters; D013599:Systole / Q000187:drug effects; D015854:Up-Regulation / Q000187:drug effects; D014882:Water-Electrolyte Balance / Q000187:drug effects
D027321:Anion Transport Proteins; D001639:Bicarbonates; D002712:Chlorides; C494849:Slc26a4 protein, mouse; D000076988:Sulfate Transporters; D012965:Sodium Chloride; D000450:Aldosterone