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, J(Cl), in mouse CCD through a pendrin-dependent mechanism. J(Cl) and 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, V-T and J(Cl) were not different from zero either in the presence or absence of angiotensin II ( 10(-8) M) in the bath. Thus further experiments employed mice given the high- NaCl diet and furosemide to upregulate renal pendrin expression. CCDs from furosemidetreated wild- type mice had a lumen- negative V-T and absorbed Cl-. With angiotensin II in the bath, Cl- absorption doubled although VT did not become more lumen negative. In contrast, in CCDs from furosemide- treated Slc26a4 null mice, Cl- secretion and a V-T of similar to 0 were observed, neither of which changed with angiotensin II application. Inhibiting ENaC with benzamil abolished V-T although JCl fell only similar to 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.