Endothelin-1 derived from spleen-activated Rho-kinase pathway in rats with secondary biliary cirrhosis.

Abstract

AIM:

  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.

CONCLUSION:

  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: Hideo Uehara, Tomohiko Akahoshi, Hirohumi Kawanaka, Naotaka Hashimoto, Yoshihiro Nagao, Morimasa Tomikawa, Akinobu Taketomi, Ken Shirabe, Makoto Hashizume, Yoshihiko Maehara
• Journal: Hepatology research : the official journal of the Japan Society of Hepatology (Hepatol Res) Vol. 42 Issue 10 Pg. 1039-47 (Oct 2012) ISSN: 1872-034X [Electronic] Netherlands
• PMID: 22594838 (Publication Type: Journal Article)
• Copyright: © 2012 The Japan Society of Hepatology.