title: Overexpression of pendrin in intercalated cells produces chloride-sensitive hypertension.
abstract: Inherited and acquired disorders that enhance the activity of transporters mediating renal tubular Na(+) reabsorption are well established causes of hypertension. It is unclear, however, whether primary activation of an Na(+)-independent chloride transporter in the kidney can also play a pathogenic role in this disease. Here, mice overexpressing the chloride transporter pendrin in intercalated cells of the distal nephron (Tg(B1-hPDS) mice) displayed increased renal absorption of chloride. Compared with normal mice, these transgenic mice exhibited a delayed increase in urinary NaCl and ultimately, developed hypertension when exposed to a high-salt diet. Administering the same sodium intake as NaHCO3 instead of NaCl did not significantly alter BP, indicating that the hypertension in the transgenic mice was chloride-sensitive. Moreover, excessive chloride absorption by pendrin drove parallel absorption of sodium through the epithelial sodium channel ENaC and the sodium-driven chloride/bicarbonate exchanger (Ndcbe), despite an appropriate downregulation of these sodium transporters in response to the expanded vascular volume and hypertension. In summary, chloride transport in the distal nephron can play a primary role in driving NaCl transport in this part of the kidney, and a primary abnormality in renal chloride transport can provoke arterial hypertension. Thus, we conclude that the chloride/bicarbonate exchanger pendrin plays a major role in controlling net NaCl absorption, thereby influencing BP under conditions of high salt intake.
authors.affiliation: Faculté de Médecine, Université Paris-Descartes, Paris, France.
authors.forename: Thibaut
authors.initials: T
authors.lastname: Jacques
authors.forename: Nicolas
authors.initials: N
authors.lastname: Picard
authors.forename: R Lance
authors.initials: RL
authors.lastname: Miller
authors.forename: Kent A
authors.initials: KA
authors.lastname: Riemondy
authors.forename: Pascal
authors.initials: P
authors.lastname: Houillier
authors.forename: Fabien
authors.initials: F
authors.lastname: Sohet
authors.forename: Suresh K
authors.initials: SK
authors.lastname: Ramakrishnan
authors.forename: Cara J
authors.initials: CJ
authors.lastname: Büsst
authors.forename: Maximilien
authors.initials: M
authors.lastname: Jayat
authors.forename: Nicolas
authors.initials: N
authors.lastname: Cornière
authors.forename: Hatim
authors.initials: H
authors.lastname: Hassan
authors.forename: Peter S
authors.initials: PS
authors.lastname: Aronson
authors.forename: Jean Christopher
authors.initials: JC
authors.lastname: Hennings
authors.forename: Christian A
authors.initials: CA
authors.lastname: Hübner
authors.forename: Raoul D
authors.initials: RD
authors.lastname: Nelson
authors.forename: Régine
authors.initials: R
authors.lastname: Chambrey
authors.forename: Dominique
authors.initials: D
authors.lastname: Eladari
mesh_terms: D000818:Animals; D001794:Blood Pressure / Q000502:physiology*; D027963:Chloride-Bicarbonate Antiporters / Q000378:metabolism*; D002712:Chlorides / Q000378:metabolism*; D006801:Humans; D006973:Hypertension / Q000378:metabolism*; D007150:Immunohistochemistry; D017136:Ion Transport; D007668:Kidney / Q000378:metabolism*; D026901:Membrane Transport Proteins / Q000378:metabolism*; D051379:Mice; D008822:Mice, Transgenic; D009399:Nephrons / Q000378:metabolism*; D012965:Sodium Chloride / Q000378:metabolism*; D000076988:Sulfate Transporters
chemical_list: D027963:Chloride-Bicarbonate Antiporters; D002712:Chlorides; D026901:Membrane Transport Proteins; C085609:SLC26A4 protein, human; D000076988:Sulfate Transporters; D012965:Sodium Chloride