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

Abstract

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 HKα2 mRNA expression in outer and inner medulla (246% and 1040%, respectively) and did not affect HKα1 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 (HKα1,2−/−). DOCP caused a similar degree of hypokalemia in WT and HKα1,2−/− mice. Importantly, WT developed metabolic alkalosis whereas HKα1,2−/− 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.