Renal water handling in rats with decompensated liver cirrhosis

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 se vere disturbances in water homeostasis: urine production was decreased and hyperosmotic, the rats had significantly decreased plasma sodium concentrat ion and ascites, and the ability to excrete an intravenous water load was s ignificantly 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-r eceptor blockade with the selective nonpeptide antagonist OPC-31260 (800 mu g.kg(-1).h(-1)) was performed during conditions whereby volume depletion wa s prevented by computer-driven, servo-controlled intravenous volume replace ment with 150 mM glucose. The aquaretic response to OPC-31260 was similar i n cirrhotic and control rats. However, the OPC 31260-induced rises in fract ional water excretion (DeltaV/GFR; +24%) and fractional distal water excret ion (DeltaV/C-Li; +46%) were significantly increased in the cirrhotic rats, where V is flow rate and Delta is change. This suggests that vasopressin-m ediated renal water reabsorption capacity was increased in the cirrhotic ra ts. Semiquantitative immunoblotting revealed that the expression of the vas opressin-regulated water channel aquaporin-2 was unchanged in membrane frac tions of both whole kidney and inner medulla from cirrhotic rats. Together, these results suggest a relative escape from vasopressin on collecting duc t water reabsorption in rats with decompensated liver cirrhosis.