title: Angiotensin II increases chloride absorption in the cortical collecting duct in mice through a pendrin-dependent mechanism.
abstract: 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(-)/HCO(3)(-) 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, V(T), 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 furosemide-treated wild-type mice had a lumen-negative V(T) and absorbed Cl(-). With angiotensin II in the bath, Cl(-) absorption doubled although V(T) did not become more lumen negative. In contrast, in CCDs from furosemide-treated Slc26a4 null mice, Cl(-) secretion and a V(T) of approximately 0 were observed, neither of which changed with angiotensin II application. Inhibiting ENaC with benzamil abolished V(T) although J(Cl) fell only approximately 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.
authors.affiliation: Renal Division, Department of Medicine, Emory University School of Medicine, Atlanta, Georgia 30322, USA. vpech@emory.edu
authors.forename: Vladimír
authors.initials: V
authors.lastname: Pech
authors.forename: Young Hee
authors.initials: YH
authors.lastname: Kim
authors.forename: Alan M
authors.initials: AM
authors.lastname: Weinstein
authors.forename: Lorraine A
authors.initials: LA
authors.lastname: Everett
authors.forename: Truyen D
authors.initials: TD
authors.lastname: Pham
authors.forename: Susan M
authors.initials: SM
authors.lastname: Wall
mesh_terms: D000584:Amiloride / Q000031:analogs & derivatives / Q000494:pharmacology; D000804:Angiotensin II / Q000494:pharmacology*; D000818:Animals; D027321:Anion Transport Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D001693:Biological Transport, Active / Q000187:drug effects; D001794:Blood Pressure / Q000187:drug effects; D001806:Blood Urea Nitrogen; D002712:Chlorides / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004848:Epithelium / Q000187:drug effects / Q000378:metabolism; D005260:Female; D005665:Furosemide / Q000494:pharmacology; D017136:Ion Transport / Q000187:drug effects; D007668:Kidney / Q000033:anatomy & histology / Q000187:drug effects; D007672:Kidney Cortex / Q000187:drug effects / Q000378:metabolism; D007685:Kidney Tubules, Collecting / Q000187:drug effects / Q000378:metabolism*; D018942:Macrolides / Q000494:pharmacology; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D018345:Mice, Knockout; D009929:Organ Size / Q000187:drug effects; D026941:Sodium Channel Blockers / Q000494:pharmacology; D012965:Sodium Chloride / Q000494:pharmacology; D000076988:Sulfate Transporters; D014662:Vasoconstrictor Agents / Q000494:pharmacology
chemical_list: D027321:Anion Transport Proteins; D002712:Chlorides; D004791:Enzyme Inhibitors; D018942:Macrolides; C494849:Slc26a4 protein, mouse; D026941:Sodium Channel Blockers; D000076988:Sulfate Transporters; D014662:Vasoconstrictor Agents; C013407:benzamil; D000804:Angiotensin II; D012965:Sodium Chloride; D000584:Amiloride; D005665:Furosemide; C040929:bafilomycin A1