Even though a hyporesponsiveness was observed in the group of patients with cirrhosis compared with the healthy group, the novel vasopressin-2 antagonist induced hypotonic diuresis in patients with cirrhosis, suggesting a therapeutic potential in managing water excess. This drug response may be a new index to assess impairment of water handling in patients with cirrhosis.
Increased activity in the hepatic sympathetic nervous system may exacerbate salt and water retention in patients with liver cirrhosis. The aim of this study was to evaluate sodium and water homeostasis in rats with cirrhosis induced by diethylnitrosamine and to investigate the influence of hepatic denervation in this model. Animals were randomized into three groups: diethylnitrosamine-treated rats with (N = 13) and without (N = 8) hepatic denervation and control rats (N = 8). Rats were fed a normal salt diet (0.23% sodium ad libitum). The 24-hr measurements for sodium balance, water balance, and creatinine clearance were performed every two weeks for 12 weeks after surgery. Diethylnitrosamine-induced cirrhosis was confirmed histologically. The cumulative change in sodium balance in the innervated diethylnitrosamine-treated rat increased progressively and was significantly higher than the control during the last four weeks of the study. Meanwhile, rats with hepatic denervation showed significantly smaller changes in cumulative sodium balance at week 12 than those in the innervated group. The cumulative changes in water balance in the innervated group were significantly greater at weeks 10 and 12 than those of the denervated and control group, which remained unchanged throughout the study. Creatinine clearance in the innervated group decreased at weeks 10 and 12 by approximately 70% from baseline (P < 0.05); in contrast, it did not change significantly in the denervated group and control group throughout the study. These results demonstrated that hepatic denervation ameliorates sodium and water retention as well as glomerular function in cirrhosis model in rats.
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