title: Sodium retention in cirrhotic rats is associated with increased renal abundance of sodium transporter proteins.
abstract: BACKGROUND
  Liver cirrhosis with ascites is associated with a decrease in renal sodium excretion and therefore sodium retention.
  
  
  METHODS
  In this paper, we utilize transporter-specific antibodies to address the hypothesis that dysregulation of one or more sodium transporters or channels is associated with sodium chloride (NaCl) retention in a rat model of cirrhosis induced by repeated exposure to carbon tetrachloride. Age-matched controls and cirrhotic rats were pair fed to ensure identical NaCl and water intake for 4 days prior to euthanasia for quantitative immunoblotting studies.
  
  
  CONCLUSIONS
  The rats manifested marked extracellular fluid volume expansion with massive ascites. Plasma aldosterone levels were markedly elevated. Analysis of immunoblots revealed marked increases in the abundances of both of the major aldosterone-sensitive apical transport proteins of the renal tubule, namely the thiazide-sensitive NaCl cotransporter NCC and the epithelial sodium channel alpha subunit (alpha-ENaC). These results are consistent with an important role for hyperaldosteronism in the pathogenesis of sodium retention and ascites formation in cirrhosis. In addition, we observed a large decrease in cortical NHE3 abundance (proximal tubule) and a large increase in NKCC2 abundance (thick ascending limb), potentially shifting premacula densa sodium absorption from proximal tubule to loop of Henle (which powers urinary concentration and dilution).
authors.affiliation: Fundació Puigvert, Renal Unit and Hypertension, Barcelona, Spain.
authors.forename: Patricia
authors.initials: P
authors.lastname: Fernández-Llama
authors.forename: Shana
authors.initials: S
authors.lastname: Ageloff
authors.forename: Guillermo
authors.initials: G
authors.lastname: Fernández-Varo
authors.forename: Josefa
authors.initials: J
authors.lastname: Ros
authors.forename: Xiaoyan
authors.initials: X
authors.lastname: Wang
authors.forename: Nuria
authors.initials: N
authors.lastname: Garra
authors.forename: Cristina
authors.initials: C
authors.lastname: Esteva-Font
authors.forename: Jose
authors.initials: J
authors.lastname: Ballarin
authors.forename: Pere
authors.initials: P
authors.lastname: Barcelo
authors.forename: Vicente
authors.initials: V
authors.lastname: Arroyo
authors.forename: John B
authors.initials: JB
authors.lastname: Stokes
authors.forename: Mark A
authors.initials: MA
authors.lastname: Knepper
authors.forename: Wladimiro
authors.initials: W
authors.lastname: Jiménez
mesh_terms: D000818:Animals; D002251:Carbon Tetrachloride / Q000633:toxicity; D004195:Disease Models, Animal; D053503:Epithelial Sodium Channels; D007668:Kidney / Q000378:metabolism*; D008106:Liver Cirrhosis, Experimental / Q000378:metabolism*; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D012964:Sodium / Q000378:metabolism*; D015222:Sodium Channels / Q000502:physiology; D000074083:Sodium-Hydrogen Exchanger 3; D017923:Sodium-Hydrogen Exchangers / Q000502:physiology; D050608:Sodium-Phosphate Cotransporter Proteins; D028021:Sodium-Potassium-Chloride Symporters / Q000502:physiology; D064466:Solute Carrier Family 12, Member 1; D027981:Symporters / Q000502:physiology
chemical_list: D053503:Epithelial Sodium Channels; C578716:Slc12a1 protein, rat; C000613387:Slc9a3 protein, rat; D015222:Sodium Channels; D000074083:Sodium-Hydrogen Exchanger 3; D017923:Sodium-Hydrogen Exchangers; D050608:Sodium-Phosphate Cotransporter Proteins; D028021:Sodium-Potassium-Chloride Symporters; D064466:Solute Carrier Family 12, Member 1; D027981:Symporters; D012964:Sodium; D002251:Carbon Tetrachloride