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Am J Physiol Renal Physiol 279: F1101-F1109, 2000;
0363-6127/00 $5.00
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Vol. 279, Issue 6, F1101-F1109, December 2000

Renal water handling in rats with decompensated liver cirrhosis

Thomas E. N. Jonassen1, Sten Christensen1, Tae-Hwan Kwon2, Susanna Langhoff1, Nanna Salling1, and Søren Nielsen2

1 Department of Pharmacology, the Panum Institute, University of Copenhagen, 2200 Copenhagen N; and the 2 Department of Cell Biology, Institute of Anatomy, University of Arhus, Arhus DK-8000, Denmark

The present study was performed to investigate the renal handling of water in rats with decompensated liver cirrhosis. Liver cirrhosis was induced by intraperitoneal administration of carbon tetrachloride twice weekly for 16 wk. Control rats were treated with vehicle. The cirrhotic rats developed severe disturbances in water homeostasis: urine production was decreased and hyperosmotic, the rats had significantly decreased plasma sodium concentration and ascites, and the ability to excrete an intravenous water load was significantly impaired. Plasma concentrations of vasopressin and aldosterone were increased. Mean arterial pressure, glomerular filtration rate (GFR), and fractional lithium excretion were decreased. Acute vasopressin type 2-receptor blockade with the selective nonpeptide antagonist OPC-31260 (800 µg · kg-1 · h-1) was performed during conditions whereby volume depletion was prevented by computer-driven, servo-controlled intravenous volume replacement with 150 mM glucose. The aquaretic response to OPC-31260 was similar in cirrhotic and control rats. However, the OPC 31260-induced rises in fractional water excretion (Delta V/GFR; +24%) and fractional distal water excretion (Delta V/CLi; +46%) were significantly increased in the cirrhotic rats, where V is flow rate and Delta  is change. This suggests that vasopressin-mediated renal water reabsorption capacity was increased in the cirrhotic rats. Semiquantitative immunoblotting revealed that the expression of the vasopressin-regulated water channel aquaporin-2 was unchanged in membrane fractions of both whole kidney and inner medulla from cirrhotic rats. Together, these results suggest a relative escape from vasopressin on collecting duct water reabsorption in rats with decompensated liver cirrhosis.

aquaporin-2; OPC-31260; collecting ducts; carbon tetrachloride; vasopressin type 2 receptor


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