The Changes Of Arginine Vasopressin And Aquaporins In Kidney/Peritoneum Of Cirrhotic Rats Complicated With Ascites And The Effects Of Terlipressin

BackgroudAscites is most prominent manifestation of decompensated liver cirrhosis, which has great influence on the life quality of the patients and induced many fatal complications.The pathological mechanism of ascites in liver cirrhosis is so complicated that it still remains unelucidated so far. At present.it is generally accepted that the plasmatic level of arginine vasopressin in cirrhotic patients usually shows remarkable increase due to the factors such as the portal hypertention, hyperkinetic circulation and the decrease of effective blood volume, which causes more water re-absorption, subsequent dilutional hyponatremia and insensitivity to common diuretics. Arginine vasopressin(AVP, antidiuretic hormone, ADH) is a major hormone in animals and humans that regulates the water-excretion function of kidneys. It is synthesized and secreted in the paraventricular nucleus and the supraoptic nucleus of hypothalamus and it is regulated by either osmostic or unosmotic factors.AVP has two types of receptorsrVl and V2 receptor. VI receptor is subdivided into two groups(VlaR and VlbR).VlaR is mainly related to the vasoconstriction, while V2R is due to the antidiuretic action of AVP which acts upon aquaporin-2 (AQP2)on collecting duct of kidneys. Besides AQP-2, the other nine kinds of aquaporins have been identified. AQP1 is distributed in the proximal tubules and descending thin limbs in kidneys and the endothelium of capillary and vein in peritoneum. Different expression of AQP1 or AQP2 in kidneys is due to the different cirrhotic rat models. There also have been few reports on the changes of AQP1 in peritoneum of the cirrhotic ascites.The management of refractory ascites and hepatorenal syndrome remains troublesome. Recent clinical trials have shown that terlipression, atroublesome. Recent clinical trials have shown that terlipression, a synthetic vasopressin analogue with long-lasting effects, can significantly increase urine volume and improve renal function in the cirrhotic patients. The mechanism needs further investigation.Part OneEstablishment of decompensated cirrhotic rat model complicated with ascitesPurpose: To establish a decompensated cirrhotic rat model complicated with ascites which is convenient and reliable with high survival rate. Methods:70 adult male SD rats whose weight was over 200g were fed with phenobarbital solution (35mg%) daily during the first week (induction phase).They were administrated with 40% CCl4-olive oil mixture by subcutaneous injection (0. 2ml/100g) twice a week for 8 weeks. Then the injections decreased to three times every two weeks for next 6 weeks. After 14 weeks, ascites was determinated by the measurement of abdomen circumference and abdominal paracentesis. 6 decompensated cirrhotic rats with 6 normal control rats were dissected .The portal vein pressure was measured by catheter insertion method. Liver specimens were obtained for pathological studies. Blood samples were obtained for liver and renal function test.Result:After 14 weeks, 37 rats survived in which 36 rats had ascites. The pathological study showed the formation of liver cirrhosis. Splennomegaly was also present. Portal vein pressure increased. Rats in normal control group showed no cirrhosis. The levels of serum total bilirubin(TB) , alanine aminotransferase(ALT) and oxalacetic transaminase (AST) were higher in cirrhotic rats than normal rats(p<0. 01) while the level of serum albumin were lower in cirrhotic rats (p<0. 05) .Conclusions: A decompensated cirrhotic rat model complicated with ascites was successfully established by improving the previous method of CC14 plus phenobarbital.