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(Hypertension. 2003;42:356.)
© 2003 American Heart Association, Inc.

Scientific Contributions

Deoxycorticosterone Upregulates PDS (Slc26a4) in Mouse Kidney

Role of Pendrin in Mineralocorticoid-Induced Hypertension

Jill W. Verlander; Kathryn A. Hassell; Ines E. Royaux; Dawn M. Glapion; Mou-Er Wang; Lorraine A. Everett; Eric D. Green; Susan M. Wall

From the Department of Medicine (J.W.V.), University of Florida College of Medicine, Gainesville; the Departments of Medicine (K.A.H., S.M.W.) and Surgery (M.-E.W.), University of Texas Medical School at Houston; the Genome Technology Branch (I.E.R., L.A.E., E.D.G.), National Human Genome Research Institute, National Institutes of Health, Bethesda, Md; the Department of Medicine (D.M.G., S.M.W.), Emory University, Atlanta, Ga; and the Wellcome Trust Sanger Institute (L.A.E.), Hinxton, Cambridge, UK.

Correspondence to Susan M. Wall, MD, Renal Division, Emory University, WMRB Rm 338, 1639 Pierce Dr NE, Atlanta, GA 30322. E-mail smwall{at}emory.edu

Pendrin is an anion exchanger expressed along the apical plasma membrane and apical cytoplasmic vesicles of type B and of non-A, non-B intercalated cells of the distal convoluted tubule, connecting tubule, and cortical collecting duct. Thus, Pds (Slc26a4) is a candidate gene for the putative apical anion-exchange process of the type B intercalated cell. Because apical anion exchange–mediated transport is upregulated with deoxycorticosterone pivalate (DOCP), we tested whether Pds mRNA and protein expression in mouse kidney were upregulated after administration of this aldosterone analogue by using quantitative real-time polymerase chain reaction as well as light and electron microscopic immunolocalization. In kidneys from DOCP-treated mice, Pds mRNA increased 60%, whereas pendrin protein expression in the apical plasma membrane increased 2-fold in non-A, non-B intercalated cells and increased 6-fold in type B cells. Because pendrin transports HCO₃^- and Cl^-, we tested whether DOCP treatment unmasks abnormalities in acid-base or NaCl balance in Pds (-/-) mice. In the absence of DOCP, arterial pH, systolic blood pressure, and body weight were similar in Pds (+/+) and Pds (-/-) mice. After DOCP treatment, weight gain and hypertension were observed in Pds (+/+) but not in Pds (-/-) mice. Moreover, after DOCP administration, metabolic alkalosis was more severe in Pds (-/-) than Pds (+/+) mice. We conclude that pendrin is upregulated with aldosterone analogues and is critical in the pathogenesis of mineralocorticoid-induced hypertension and metabolic alkalosis.

Key Words: acid-base equilibrium • hypertension, mineralocorticoid • anions • mice • ion transport

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