title: Ciclosporin-induced hypertension is associated with increased sodium transporter of the loop of Henle (NKCC2).
abstract: BACKGROUND
  Hypertension induced by cyclosporine is associated with renal sodium and water retention. Using immunoblotting of kidney homogenates, we investigated the regulation of sodium and water transport proteins in a rat model of cyclosporine-induced hypertension.
  
  
  METHODS
  Rats were treated with cyclosporine (25 mg/kg/day intraperitoneally) during 7 days. Control rats received vehicle.
  
  
  RESULTS
  Cyclosporine-treated rats had an increase in blood pressure with a decrease in renal sodium excretion compared with control rats. There were no differences either in sodium intake or in plasma creatinine levels between the two groups of rats. These data suggest that the decrease in sodium excretion in the cyclosporine-treated rats was due to an increase in renal sodium absorption. The densitometric analysis of the renal immunoblot showed an increase in the Na-K-2Cl cotransporter of the loop of Henle (NKCC2) in cyclosporine-treated rats (178% +/- 36) compared with control rats (100% +/- 18; P < 0.05*). This protein rise was associated with an increase in the NKCC2 mRNA pointing to a transcriptional regulation of this sodium transporter. There were no statistically significant changes in the sodium proton exchange (NHE-3) of the proximal tubule although in this renal segment, aquaporin-1 was increased in cyclosporine-treated rats compared with control rats (control 100% +/- 6 vs cyclosporine 119% +/- 6; P < 0.05*).
  
  
  CONCLUSIONS
  Our results pointed to the thick ascending limb of the loop of Henle as an important site of sodium retention in cyclosporine-induced hypertension. This data may have potential clinical implications for the treatment of hypertension induced by cyclosporine.
authors.affiliation: Fundació Puigvert, Cartagena 340-350, 08025 Barcelona, Spain.
authors.forename: Cristina
authors.initials: C
authors.lastname: Esteva-Font
authors.forename: Elisabet
authors.initials: E
authors.lastname: Ars
authors.forename: Elena
authors.initials: E
authors.lastname: Guillen-Gomez
authors.forename: Josep Maria
authors.initials: JM
authors.lastname: Campistol
authors.forename: Laia
authors.initials: L
authors.lastname: Sanz
authors.forename: Wladimiro
authors.initials: W
authors.lastname: Jiménez
authors.forename: Mark Alan
authors.initials: MA
authors.lastname: Knepper
authors.forename: Ferran
authors.initials: F
authors.lastname: Torres
authors.forename: Roser
authors.initials: R
authors.lastname: Torra
authors.forename: José Aurelio
authors.initials: JA
authors.lastname: Ballarín
authors.forename: Patricia
authors.initials: P
authors.lastname: Fernández-Llama
mesh_terms: D000818:Animals; D001692:Biological Transport; D016572:Cyclosporine / Q000494:pharmacology*; D004195:Disease Models, Animal; D006973:Hypertension / Q000188:drug therapy*; D007166:Immunosuppressive Agents / Q000494:pharmacology; D007668:Kidney / Q000378:metabolism; D008138:Loop of Henle / Q000378:metabolism; D008954:Models, Biological; D051381:Rats; D017208:Rats, Wistar; D012964:Sodium / Q000378:metabolism*; D000074083:Sodium-Hydrogen Exchanger 3; D017923:Sodium-Hydrogen Exchangers; D028021:Sodium-Potassium-Chloride Symporters / Q000378:metabolism / Q000502:physiology*; D064466:Solute Carrier Family 12, Member 1; D014867:Water / Q000378:metabolism
chemical_list: D007166:Immunosuppressive Agents; C578716:Slc12a1 protein, rat; C000613387:Slc9a3 protein, rat; D000074083:Sodium-Hydrogen Exchanger 3; D017923:Sodium-Hydrogen Exchangers; D028021:Sodium-Potassium-Chloride Symporters; D064466:Solute Carrier Family 12, Member 1; D014867:Water; D016572:Cyclosporine; D012964:Sodium