title: Endothelin-1 derived from spleen-activated Rho-kinase pathway in rats with secondary biliary cirrhosis.
abstract: OBJECTIVE
  Splenectomy or partial splenic embolism has been reported to improve liver function in patients with hypersplenism and liver dysfunction. The aim of this study was to investigate the mechanism of improvement after splenectomy.
  
  
  METHODS
  Liver cirrhosis was induced by bile duct ligation (BDL). Rats underwent sham operation, splenectomy (Sp group), BDL, or BDL plus splenectomy (BDL + Sp group), and were subjected to experiments at 2 weeks after the operation. Portal venous pressure (PVP) and hepatic tissue blood flow (HTBF) were measured in each group. The plasma concentration of endothelin-1 (ET-1) and endothelial nitric oxide synthase (eNOS), RhoA and Rho-kinase expressions were studied.
  
  
  RESULTS
  There were significant differences in PVP (17.9 ± 0.91 vs 23.3 ± 3.91 cmH(2) O; P < 0.01) and HTBF (16.6 ± 1.72 vs 13.3 ± 1.82 mL/min; P < 0.01) between the BDL + Sp and BDL groups. In the liver of BDL rats, eNOS phosphorylation and NOx levels were decreased, accompanied by RhoA activation compared with the BDL + Sp group. Splenectomy decreased serum ET-1 levels, RhoA activation and consequently increased eNOS phosphorylation.
  
  
  CONCLUSIONS
  ET-1 derived from the spleen might increase intrahepatic resistance by downregulating Rho signaling in liver cirrhosis. Splenectomy for splenomegaly in liver cirrhosis might partially improve liver function by enhancing intrahepatic microcirculation.
authors.affiliation: Departments of Surgery and Science             Disaster and Emergency Medicine, Graduate School of Medical Science, Kyushu University, Fukuoka, Japan.
authors.forename: Hideo
authors.initials: H
authors.lastname: Uehara
authors.forename: Tomohiko
authors.initials: T
authors.lastname: Akahoshi
authors.forename: Hirohumi
authors.initials: H
authors.lastname: Kawanaka
authors.forename: Naotaka
authors.initials: N
authors.lastname: Hashimoto
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Nagao
authors.forename: Morimasa
authors.initials: M
authors.lastname: Tomikawa
authors.forename: Akinobu
authors.initials: A
authors.lastname: Taketomi
authors.forename: Ken
authors.initials: K
authors.lastname: Shirabe
authors.forename: Makoto
authors.initials: M
authors.lastname: Hashizume
authors.forename: Yoshihiko
authors.initials: Y
authors.lastname: Maehara