Angiotensin II increases chloride absorption in the cortical collecting duct in mice through a pendrin-dependent mechanism

Pendrin ( Slc26a4) localizes to type B and non-A, non-B intercalated cells in the distal convoluted tubule, the connecting tubule, and the cortical collecting duct (CCD), where it mediates apical Cl−/HCO3−exchange. The purpose of this study was to determine whether angiotensin II increases transepithelial net chloride transport, JCl, in mouse CCD through a pendrin-dependent mechanism. JCland transepithelial voltage, VT, were measured in CCDs perfused in vitro from wild-type and Slc26a4 null mice ingesting a NaCl-replete diet or a NaCl-replete diet and furosemide. In CCDs from wild-type mice ingesting a NaCl-replete diet, VTand JClwere not different from zero either in the presence or absence of angiotensin II (10−8M) in the bath. Thus further experiments employed mice given the high-NaCl diet and furosemide to upregulate renal pendrin expression. CCDs from furosemide-treated wild-type mice had a lumen-negative VTand absorbed Cl−. With angiotensin II in the bath, Cl−absorption doubled although VTdid not become more lumen negative. In contrast, in CCDs from furosemide-treated Slc26a4 null mice, Cl−secretion and a VTof ∼0 were observed, neither of which changed with angiotensin II application. Inhibiting ENaC with benzamil abolished VTalthough JClfell only ∼50%. Thus substantial Cl−absorption is observed in the absence of an electromotive force. Attenuating apical anion exchange with the peritubular application of the H+-ATPase inhibitor bafilomycin abolished benzamil-insensitive Cl−absorption. In conclusion, angiotensin II increases transcellular Cl−absorption in the CCD through a pendrin- and H+-ATPase-dependent process.