title: Tolvaptan regulates aquaporin-2 and fecal water in cirrhotic rats with ascites.
abstract: OBJECTIVE
  To investigate the role of tolvaptan in regulating aquaporin (AQP)-2 expression and fecal water content in cirrhotic rats with ascites.
  
  
  METHODS
  Cirrhosis with ascites was induced in rats by repetitive dorsal injection of CCl4 for 14 wk. In total, 84 cirrhotic rats with ascites divided into three groups (vehicle, 3 mg/kg and 5 mg/kg tolvaptan), and then further divided into five subgroups (days 1, 2, 3, 4, and 5). Blood samples were obtained to measure vasopressin and sodium concentrations. Rats were killed and colonic mucosa was scraped for analysis of protein expression and AQP-2 transcriptional level. The whole layer was fixed for hematoxylin&eosin (HE) staining and feces were collected for determination of fecal water content.
  
  
  CONCLUSIONS
  Compared with vehicle, vasopressin decreased significantly in the tolvaptan groups from day 2 to a similar level in each treatment group. AQP-2 showed significant upregulation in cirrhotic rats with ascites compared with an untreated control group (100% ± 22.9% vs 22.2% ± 10.23%, P < 0.01). After administration of tolvaptan, AQP-2 expression began to decrease significantly from day 2 in each treatment group, but no significant difference was finally found between the treatment groups. Fecal water content in the distal colon was increased by 5 mg/kg tolvaptan on day 1 (66.8% ± 9.3% vs 41.4% ± 6.3%, in the vehicle group, P < 0.05). Fecal water content returned to baseline at day 4 at the latest in both treatment groups, and did not correspond to the change in AQP-2 expression. HE staining of the colonic mucosa showed no mucosal damage related to tolvaptan.
  
  
  CONCLUSIONS
  Upregulation of AQP-2 in the distal colon is found in cirrhotic rats with ascites. Tolvaptan inhibits its expression and may decrease water reabsorption and induce diarrhea.
authors.affiliation: Chao Chen, Ren-Pin Chen, Hai-Hua Lin, Wen-You Zhang, Xie-Lin Huang, Zhi-Ming Huang, Department of Gastroenterology, the First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, Zhejiang Province, China.
authors.forename: Chao
authors.initials: C
authors.lastname: Chen
authors.affiliation: Chao Chen, Ren-Pin Chen, Hai-Hua Lin, Wen-You Zhang, Xie-Lin Huang, Zhi-Ming Huang, Department of Gastroenterology, the First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, Zhejiang Province, China.
authors.forename: Ren-Pin
authors.initials: RP
authors.lastname: Chen
authors.affiliation: Chao Chen, Ren-Pin Chen, Hai-Hua Lin, Wen-You Zhang, Xie-Lin Huang, Zhi-Ming Huang, Department of Gastroenterology, the First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, Zhejiang Province, China.
authors.forename: Hai-Hua
authors.initials: HH
authors.lastname: Lin
authors.affiliation: Chao Chen, Ren-Pin Chen, Hai-Hua Lin, Wen-You Zhang, Xie-Lin Huang, Zhi-Ming Huang, Department of Gastroenterology, the First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, Zhejiang Province, China.
authors.forename: Wen-You
authors.initials: WY
authors.lastname: Zhang
authors.affiliation: Chao Chen, Ren-Pin Chen, Hai-Hua Lin, Wen-You Zhang, Xie-Lin Huang, Zhi-Ming Huang, Department of Gastroenterology, the First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, Zhejiang Province, China.
authors.forename: Xie-Lin
authors.initials: XL
authors.lastname: Huang
authors.affiliation: Chao Chen, Ren-Pin Chen, Hai-Hua Lin, Wen-You Zhang, Xie-Lin Huang, Zhi-Ming Huang, Department of Gastroenterology, the First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, Zhejiang Province, China.
authors.forename: Zhi-Ming
authors.initials: ZM
authors.lastname: Huang
mesh_terms: D000818:Animals; D051399:Aquaporin 2 / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D001201:Ascites / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism; D001552:Benzazepines / Q000494:pharmacology* / Q000633:toxicity; D002251:Carbon Tetrachloride; D003106:Colon / Q000187:drug effects* / Q000378:metabolism; D003967:Diarrhea / Q000139:chemically induced / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005243:Feces / Q000737:chemistry*; D008106:Liver Cirrhosis, Experimental / Q000139:chemically induced / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism; D008297:Male; D017207:Rats, Sprague-Dawley; D012964:Sodium / Q000097:blood; D013997:Time Factors; D000077602:Tolvaptan; D014667:Vasopressins / Q000097:blood; D014867:Water / Q000378:metabolism*
chemical_list: C496025:Aqp2 protein, rat; D051399:Aquaporin 2; D001552:Benzazepines; D014867:Water; D014667:Vasopressins; D000077602:Tolvaptan; D012964:Sodium; D002251:Carbon Tetrachloride
keywords: Aquaporin-2; Ascites; Cirrhosis; Tolvaptan