Mineralocorticoids stimulate the activity and expression of renal H,K‐ATPases

Mineralocorticoids such as deoxycorticosterone activate Na + reabsorption and H + secretion in the renal collecting duct. In this study, the effect of deoxycorticosterone pivalate (DOCP) on renal H + ,K + ‐ATPase activity and expression was investigated. Eight days after female wild type (WT) mice received DOCP, collecting ducts were perfused in vitro to measure H + ,K + ‐ATPase‐dependent H + secretion after an acute intracellular acid load. DOCP stimulated H + ,K + ‐ATPase mediated H + secretion in A type intercalated cells of inner cortical collecting ducts by 70% whereas no effect of DOCP was observed in B type intercalated cells compared to control. DOCP dramatically increased HKα 2 mRNA expression in outer and inner medulla (246% and 1040%, respectively) and did not affect HKα 1 mRNA expression. DOCP treatment caused significant body weight gain in WT mice and had little effect on body weight in mice lacking both α subunits (HKα 1,2 −/− ). DOCP caused a similar degree of hypokalemia in WT and HKα 1,2 −/− mice. Importantly, WT developed metabolic alkalosis whereas HKα 1,2 −/− mice did not. In summary, these data clearly demonstrate a physiological role for renal H + ,K + ‐ATPases in mineralocorticoid stimulated H + secretion and suggest a role for these enzymes in Na + reabsorption. Studies were funded by NIH RO1‐DK‐049750 to C.S.W and 5T32DK007518‐22 to M.M.G.