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.

RESULTS AND CONCLUSION:

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: Patricia Fernández-Llama, Shana Ageloff, Guillermo Fernández-Varo, Josefa Ros, Xiaoyan Wang, Nuria Garra, Cristina Esteva-Font, Jose Ballarin, Pere Barcelo, Vicente Arroyo, John B Stokes, Mark A Knepper, Wladimiro Jiménez
• Journal: Kidney international (Kidney Int) Vol. 67 Issue 2 Pg. 622-30 (Feb 2005) ISSN: 0085-2538 [Print] United States
• PMID: 15673309 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S., Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Epithelial Sodium Channels
• Slc12a1 protein, rat
• Slc9a3 protein, rat
• Sodium Channels
• Sodium-Hydrogen Exchanger 3
• Sodium-Hydrogen Exchangers
• Sodium-Phosphate Cotransporter Proteins
• Sodium-Potassium-Chloride Symporters
• Solute Carrier Family 12, Member 1
• Symporters
• Sodium
• Carbon Tetrachloride

Topics

• Animals
• Carbon Tetrachloride (toxicity)
• Disease Models, Animal
• Epithelial Sodium Channels
• Kidney (metabolism)
• Liver Cirrhosis, Experimental (metabolism)
• Male
• Rats
• Rats, Wistar
• Sodium (metabolism)
• Sodium Channels (physiology)
• Sodium-Hydrogen Exchanger 3
• Sodium-Hydrogen Exchangers (physiology)
• Sodium-Phosphate Cotransporter Proteins
• Sodium-Potassium-Chloride Symporters (physiology)
• Solute Carrier Family 12, Member 1
• Symporters (physiology)