Pendrin is upregulated with loop diuretics and is critical to the maintenance of fluid and electrolyte balance.

Abstract

Pendrin, encoded by the Slc26a4 gene, is a Cl−/HCO3− exchanger which is highly expressed in the apical regions of type B and non-A, non-B intercalated cells of kidney. Pendrin-mediated Cl− absorption is critical in maintaining vascular volume, blood pressure and acid-base homeostasis and is thought to be regulated through changes in renal distal Cl− delivery. Thus, pendrin expression and its role in maintaining fluid and electrolyte balance were studied in wild type and Slc26a4 null mice given high NaCl diet alone (HS) or the high NaCl diet (1.1 meq/day NaCl) plus the loop diuretic, furosemide (100 μg /g BW per day, HS + F), using immunohistochemistry and balance studies. In wild type mice, type B and non-A, non-B cell size and pendrin immunolabel increased dramatically in kidneys from furosemide-treated mice. Moreover, furosemide-treated Slc26a4 null mice had much greater apparent vascular volume contraction than wild type mice either following ingestion of the high NaCl diet alone or the high NaCl diet and furosemide. Conclusions Pendrin expression increases markedly in mice treated with a high NaCl diet and furosemide, despite an expected increase in distal Cl− delivery. In this model, pendrin is critical in the maintenance of intravascular volume.