Tolvaptan regulates aquaporin-2 and fecal water in cirrhotic rats with ascites
AIM: To investigate the role of tolvaptan in regulating aquaporin (AQP)-2 expression and fecal water content in cirrhotic rats with ascites.METHODS: Cirrhotic rats with ascites were induced by repetitive dorsal injection of CCl4 for 14 wk.In total, 84 cirrhotic rats with ascites treated with tolvaptan were divided into three groups (vehicle, and 3 mg/kg and 5 mg/kg tolvaptan), and then further grouped into five subgroups (days i, 2, 3, 4 and 5).Rats were killed after administration of tolvaptan, and blood samples were obtained to measure vasopressin and sodium concentrations.Colonic mucosa was scraped for protein expression and transcriptional level of aquaporin-2.The whole layer was fixed for hematoxylin-eosin (HE) staining and feces were collected for calculation of fecal water content.RESULTS: Vasopressin decreased compared to the vehicle group from day 2, but eventually reached a similar level in each treatment group, despite the different doses of tolvaptan.AQP-2 showed significant upregulation in cirrhotic rats with ascites compared to the control group (100 ± 17.23% vs 22.2 ± 10.23%;P <0.01).After administration of tolvaptan, expression of AQP-2 began to decrease from day 2 in each treatment group, but no significant difference was found finally.Fecal water content in the distal colon was increased by 5 mg/kg tolvaptan on day 1 (67.3 ± 4.32% vs 42.2 ± 5.26% in the vehicle group;P <0.05).Fecal water content returned to the baseline at day 4 at the latest, and it was not correspondent with the change of AQP-2 expression.HE staining of colonic mucosa was also utilized, but no mucosal damage was detected.CONCLUSIONS: Upregulation of AQP-2 in distal colon is found in cirrhotic rats with ascites.Tolvaptan inhibits its expression and might decrease water reabsorption and induce diarrhea.
Tolvaptan Aquaporin-2 Cirrhosis Ascites Fecal water content
Huang Zhiming Chao Chen Ren-Pin Chen Hai-Hua Lin Wen-You Zhang Xie-Lin Huang
Department of Gastroenterology,The First Affiliated Hospital of Wenzhou Medical University,Wenzhou 3 Department of Gastroenterology,The First Affiliated Hospital of Wenzhou Medical University,Wenzhou 3
国内会议
第八届浙江国际消化病学术大会暨美国胃肠病协会第二届中国学术论坛
浙江绍兴
英文
194-205
2015-10-30（万方平台首次上网日期，不代表论文的发表时间）