Angiotensin II Activates H+-ATPase in Type A Intercalated Cells

Abstract

We reported previously that angiotensin II (AngII) increases net Cl⁻ absorption in mouse cortical collecting duct (CCD) by transcellular transport across type B intercalated cells (IC) via an H⁺-ATPase–and pendrin-dependent mechanism. Because intracellular trafficking regulates both pendrin and H⁺-ATPase, we hypothesized that AngII induces the subcellular redistribution of one or both of these exchangers. To answer this question, CCD from furosemide-treated mice were perfused in vitro, and the subcellular distributions of pendrin and the H⁺-ATPase were quantified using immunogold cytochemistry and morphometric analysis. Addition of AngII in vitro did not change the distribution of pendrin or H⁺-ATPase within type B IC but within type A IC increased the ratio of apical plasma membrane to cytoplasmic H⁺-ATPase three-fold. Moreover, CCDs secreted bicarbonate under basal conditions but absorbed bicarbonate in response to AngII. In summary, angiotensin II stimulates H⁺ secretion into the lumen, which drives Cl⁻ absorption mediated by apical Cl⁻/HCO₃⁻ exchange as well as generates more favorable electrochemical gradient for ENaC-mediated Na⁺ absorption.