Dysregulation of renal aquaporins and Na-Cl cotransporter in CCl4-induced cirrhosis

Kidney Int. 2000 Jul;58(1):216-28. doi: 10.1046/j.1523-1755.2000.00156.x.


Background: Severe hepatic cirrhosis is associated with abnormal renal water retention.

Methods: Semiquantitative immunoblotting was employed to investigate the abundance of the major renal aquaporins (water channels) and sodium-dependent cotransporters in kidneys from control rats and rats with cirrhosis secondary to chronic CCl4 inhalation.

Results: The cirrhotic rats had ascites and manifested a water excretion defect detected by a standard water-loading test. The abundance of aquaporin-1 (the major aquaporin in the proximal tubule) was increased, an effect markedly accentuated in high-density membrane fractions prepared by differential centrifugation. Differential centrifugation studies demonstrated a redistribution of aquaporin-2 from high-density to low-density membranes, compatible with increased trafficking of aquaporin-2 to the plasma membrane. The abundance of aquaporin-3, but not aquaporin-2, was increased in collecting ducts of rats with CCl4-induced cirrhosis. The Na-K-2Cl cotransporter of the thick ascending limb showed no change in abundance. However, the abundance of the thiazide-sensitive Na-Cl cotransporter of the distal convoluted tubule was markedly suppressed in cirrhotic rats, possibly contributing to a defect in urinary dilution.

Conclusions: In this model of cirrhosis, the development of a defect in urinary dilution may be multifactorial, with contributions from at least four abnormalities in transporter regulation: (1) an increase in the renal abundance of aquaporin-1, (2) a cellular redistribution of aquaporin-2 in the collecting duct compatible with trafficking to the plasma membrane without an increase in total cellular aquaporin-2, (3) an increase in the renal abundance of aquaporin-3, and (4) a decrease in the abundance of the thiazide-sensitive cotransporter of the distal convoluted tubule.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Aquaporin 1
  • Aquaporin 2
  • Aquaporin 3
  • Aquaporin 6
  • Aquaporins / analysis
  • Aquaporins / metabolism*
  • Carbon Tetrachloride
  • Carrier Proteins / analysis
  • Carrier Proteins / metabolism*
  • Chlorides / metabolism
  • Immunoblotting
  • Kidney Concentrating Ability / physiology
  • Kidney Tubules / metabolism*
  • Kidney Tubules, Collecting / metabolism
  • Kidney Tubules, Distal / metabolism
  • Kidney Tubules, Proximal / metabolism
  • Liver Cirrhosis, Experimental / chemically induced
  • Liver Cirrhosis, Experimental / metabolism*
  • Male
  • Rats
  • Rats, Wistar
  • Sodium / metabolism
  • Sodium Chloride Symporters
  • Symporters*


  • Aqp1 protein, rat
  • Aqp2 protein, rat
  • Aqp3 protein, rat
  • Aquaporin 2
  • Aquaporin 6
  • Aquaporins
  • Carrier Proteins
  • Chlorides
  • Sodium Chloride Symporters
  • Symporters
  • Aquaporin 1
  • Aquaporin 3
  • Sodium
  • Carbon Tetrachloride