Increased gene expression of water channel in cirrhotic rat kidneys



In patients with liver cirrhosis, impaired water and sodium excretion has been incriminated in the pathogenesis of ascites formation. Increased reabsorption of water in the distal nephron has been shown to play an important role in water retention in cirrhotic rat kidneys. Recently, a complementary DNA (cDNA) for the vasopressin-regulated water channel (the aquaporin of the apical membrane of the kidney collecting duct [AQP-CD]) has been cloned. It is suggested that AQP-CD plays an important role in renal water handling. Therefore, in the present study, to investigate the pathogenic role of the water channel in water retention in liver cirrhosis, gene expression of AQP-CD in the kidney was evaluated in cirrhotic rats. Liver cirrhosis was induced by an intraperitoneal administration of carbon tetrachloride twice a week for 12 weeks in 14 rats. Messenger RNA expression of AQP-CD in whole kidney homogenates determined by northern blot hybridization was significantly increased in cirrhotic rats (147%; P<.01) and dehydrated rats (206%; P<.0001) compared with control rats. Protein expression of AQP-CD in the homogenates of kidney medulla determined by Western blot analysis was significantly increased in cirrhotic rats (203%; P<.03) compared with control rats. Furthermore, mRNA expression of AQP-CD in the kidney showed a significant correlation with the volume of ascites in cirrhotic rats (r = 0.62, P<.02). No significant difference was observed in water intake, urinary volume, serum osmolality, serum sodium, and creatinine clearance between control and cirrhotic rats, suggesting that dehydration was unlikely in cirrhotic rats. From these results, it is concluded that renal mRNA expression of AQP-CD plays an important role in abnormal water retention followed by the development of ascites in liver cirrhosis. (Hepatology 1995;21:169–173).