title: Angiotensin II acts through the angiotensin 1a receptor to upregulate pendrin.
abstract: Pendrin is an anion exchanger expressed in the apical regions of B and non-A, non-B intercalated cells. Since angiotensin II increases pendrin-mediated Cl(-) absorption in vitro, we asked whether angiotensin II increases pendrin expression in vivo and whether angiotensin-induced hypertension is pendrin dependent. While blood pressure was similar in pendrin null and wild-type mice under basal conditions, following 2 wk of angiotensin II administration blood pressure was 31 mmHg lower in pendrin null than in wild-type mice. Thus pendrin null mice have a blunted pressor response to angiotensin II. Further experiments explored the effect of angiotensin on pendrin expression. Angiotensin II administration shifted pendrin label from the subapical space to the apical plasma membrane, independent of aldosterone. To explore the role of the angiotensin receptors in this response, pendrin abundance and subcellular distribution were examined in wild-type, angiotensin type 1a (Agtr1a) and type 2 receptor (Agtr2) null mice given 7 days of a NaCl-restricted diet (< 0.02% NaCl). Some mice received an Agtr1 inhibitor (candesartan) or vehicle. Both Agtr1a gene ablation and Agtr1 inhibitors shifted pendrin label from the apical plasma membrane to the subapical space, independent of the Agtr2 or nitric oxide (NO). However, Agtr1 ablation reduced pendrin protein abundance through the Agtr2 and NO. Thus angiotensin II-induced hypertension is pendrin dependent. Angiotensin II acts through the Agtr1a to shift pendrin from the subapical space to the apical plasma membrane. This Agtr1 action may be blunted by the Agtr2, which acts through NO to reduce pendrin protein abundance.
authors.affiliation: Renal Division, Emory University School of Medicine, 1639 Pierce Dr. NE, Atlanta, GA 30322, USA.
authors.forename: Jill W
authors.initials: JW
authors.lastname: Verlander
authors.forename: Seongun
authors.initials: S
authors.lastname: Hong
authors.forename: Vladimir
authors.initials: V
authors.lastname: Pech
authors.forename: James L
authors.initials: JL
authors.lastname: Bailey
authors.forename: Diana
authors.initials: D
authors.lastname: Agazatian
authors.forename: Sharon W
authors.initials: SW
authors.lastname: Matthews
authors.forename: Thomas M
authors.initials: TM
authors.lastname: Coffman
authors.forename: Thu
authors.initials: T
authors.lastname: Le
authors.forename: Tadashi
authors.initials: T
authors.lastname: Inagami
authors.forename: Florence M
authors.initials: FM
authors.lastname: Whitehill
authors.forename: I David
authors.initials: ID
authors.lastname: Weiner
authors.forename: Donna B
authors.initials: DB
authors.lastname: Farley
authors.forename: Young Hee
authors.initials: YH
authors.lastname: Kim
authors.forename: Susan M
authors.initials: SM
authors.lastname: Wall
mesh_terms: D000450:Aldosterone / Q000494:pharmacology; D000804:Angiotensin II / Q000494:pharmacology; D047228:Angiotensin II Type 1 Receptor Blockers / Q000494:pharmacology; D000818:Animals; D027321:Anion Transport Proteins / Q000378:metabolism*; D001562:Benzimidazoles / Q000494:pharmacology; D001713:Biphenyl Compounds; D001794:Blood Pressure / Q000187:drug effects; D004039:Diet, Sodium-Restricted; D005260:Female; D006973:Hypertension / Q000139:chemically induced / Q000378:metabolism*; D008297:Male; D051379:Mice; D009569:Nitric Oxide / Q000378:metabolism; D044140:Receptor, Angiotensin, Type 1 / Q000235:genetics / Q000378:metabolism*; D044139:Receptor, Angiotensin, Type 2 / Q000378:metabolism; D000076988:Sulfate Transporters; D013777:Tetrazoles / Q000494:pharmacology; D015854:Up-Regulation; D014662:Vasoconstrictor Agents / Q000494:pharmacology
chemical_list: C544066:Agtr1a protein, mouse; D047228:Angiotensin II Type 1 Receptor Blockers; D027321:Anion Transport Proteins; D001562:Benzimidazoles; D001713:Biphenyl Compounds; D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2; C494849:Slc26a4 protein, mouse; D000076988:Sulfate Transporters; D013777:Tetrazoles; D014662:Vasoconstrictor Agents; D000804:Angiotensin II; D009569:Nitric Oxide; D000450:Aldosterone; C081643:candesartan