Long-term aldosterone administration increases renal Na+-Cl− cotransporter abundance in late distal convoluted tubule

Søren Brandt Poulsen, Birgitte Mønster Christensen
2017 AJP - Renal Physiology  
Poulsen SB, Christensen BM. Long-term aldosterone administration increases renal Na ϩ -Cl Ϫ cotransporter abundance in late distal convoluted tubule. Na ϩ -Cl Ϫ cotransporter (NCC) is expressed in early distal convoluted tubule (DCT) 1 and late DCT (DCT2). NCC activity can be stimulated by aldosterone administration, and the mechanism is assumed to depend on the enzyme 11␤-hydroxysteroid dehydrogenase type 2 (11␤-HSD2), which inactivates glucocorticoids that would otherwise occupy aldosterone
more » ... ccupy aldosterone receptors. Because 11␤-HSD2 in rat may only be abundantly expressed in DCT2 cells and not in DCT1 cells, it has been speculated that aldosterone specifically stimulates NCC activity in DCT2 cells. In mice, however, it is debated if 11␤-HSD2 is expressed in DCT2 cells. The present study examined whether aldosterone administration in mice stimulates NCC abundance and phosphorylation in DCT2 cells but not in DCT1 cells. B6/C57 male mice were administered 100 g aldosterone·kg body weight Ϫ1 ·24 h Ϫ1 for 6 days and euthanized during isoflurane inhalation. Western blotting of whole kidney homogenate showed that aldosterone administration stimulated NCC and pT58-NCC abundances (P Ͻ 0.001). In DCT1 cells, confocal microscopy detected no effect of the aldosterone administration on NCC and pT58-NCC abundances. By contrast, NCC and pT58-NCC abundances were stimulated by aldosterone administration in the middle of DCT2 (P Ͻ 0.001 and Ͻ0.01, respectively) and at the junction between DCT2 and CNT (P Ͻ 0.001 and Ͻ0.05, respectively). In contrast to rat, immunohistochemistry in mouse showed no/very weak 11␤-HSD2 expression in DCT2 cells. Collectively, long-term aldosterone administration stimulates mouse NCC and pT58-NCC abundances in DCT2 cells and presumably not in DCT1 cells. epithelial sodium channel; hyperaldosteronism; thiazide-sensitive Na ϩ -Cl Ϫ cotransporter; mineralocorticoid receptor; sodium and chloride reabsorption * S. B. Poulsen and B. M. Christensen contributed equally to this work.
doi:10.1152/ajprenal.00352.2016 pmid:27733368 fatcat:4w4youoezrajhdnlsf7hsiwrxi