Evidence for Aldosterone‐mediated regulation of Na‐K ATPase in kidney proximal tubules

Abstract

Recent investigations from several laboratories have shown MR expression and increased NHE3, NHE1, and NBCe1 activities in kidney proximal tubules (PT) after aldosterone (Aldo) stimulation. Non‐genomic effects of Aldo have been demonstrated in human kidney PT cells (HK‐2). We hypothesize that Aldo increases Na+/K+ ATPase (Na/K) activity in PT. In the present study we aim to 1) determine if MR is present in human and rat kidney PT 2) determine if Aldo regulates Na/K expression and activity in rat basolateral membranes 3) determine if Aldo increases Na/K subunit in human kidney PT cells. IHC analysis of human and rat kidneys showed presence of MR in PT. Adrenalectomy (ADX) resulted in decreased MR, Na/K, and NHE1 in PT and β and γ ENaC in DCT and CCD. Treatment with Aldo restored MR, Na/K, and NHE1 expression in PT and ENaC expression in DCT and CCD. In human kidney PT cells (HK2, HKC‐5,‐8, and ‐11) Aldo caused translocation of MR into nucleus. Aldo increased Na/K expression and activity in human kidney PT cells. The effects of Aldo on Na/K activity in human kidney PT cells was blocked by specific inhibitors of MR (spironolactone) and by 11β‐HSD inhibitor carbonexolone but not by a GR inhibitor (mifepristone). Treatment with Aldo resulted in decrease in intracellular pH in human kidney PT cells. These results suggest that Aldo may regulate Na/K and NHE1 expression and activity in human and rat kidney PT.Funded by VAMR and AHA