| Budget Amount *help |
¥1,500,000 (Direct Cost: ¥1,500,000)
Fiscal Year 1995: ¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 1994: ¥700,000 (Direct Cost: ¥700,000)
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| Research Abstract |
It has been wall documented that the liver contains many receptors, which involve the osmoreceptor, baroreceptor, NaCl receptor and glucose receptor. Recently, we have demonstrated that an increase in NaCl concentration in the hepatic portal vein reflexively decreases jejunal NaCl absorption and increases urinary NaCl excretion. Afferent pathway of these reflexes is the hepatic nerves and efferent pathways are the cholinergic nerves to the jejunum and the renal sympathetic nerve, respectively. Furthermore, a high NaCl food intake elicits a decrease in renal nerve activity and then a natriuresis. The decrease in renal nerve activity is completely abolished by hepatic denervation. These results indicate that the hepatic nerves have a significant role in regulation of NaCl homeostasis. However, it is still unclear whether the hepatic nerves play a significant role in regulating long-term NaCl homeostasis. Accordingly, the purpose of the present study was to examine the long-term role of t
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he hepatic nerves in regulating NaCl homeostasis. To examine this, rats with or without the hepatic nerves were kept in metabolic cages and NaCl balance was measured for 40 days continuously. Furthermore, sensitivity of the hepatic Na sensitive mechanism was measured in normal rats and rats with liver cirrhosis.
The effect of hepatic denervation on NaCl balance was examined. When rats were fed normal NaCl food (0.45% NaCl), hepatic denervation had no significant effect on NaCl balance. However, when rats were fed hegh NaCl food (8% NaCl for 10 days), NaCl balance become more positive in hepatic denervated rats than in sham rats. Thus, the hepatic nerves play a significant role in the long-term control of NaCl balance.
The sensitivity of the hepatoportal Na sensitive mechanism was measured in rats with CCl_4-induced liver cirrhosis. In normal rats, the activity of the hepatoportal Na sensitive afferent nerves was increased by portal injection of hypertonic NaCl solution. This effect was markedly reduced in rats with CCl_4-induced liver cirrhosis. Liver tissue norepinephrine content, a marker of tissue innervation, was also decreased in rats with liver cirrhosis. Over the 12 wk CCl_4-treatment period, no significant difference in Na balance was found between control and cirrhosis rats when both groups were given normal NaCl food. However, when both were given high NaCl food, the Na balance of cirrhosis rats was positive and greater than that of control. These results indicate that the sensitivity of the hepatoportal NaCl receptors is decreased even when the degree of liver cirrhosis is slight. This mechanism plays an important role in maintaining Na balance during intake of high NaCl food. Less
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