Mechanisms Involved in the Contraction of Intrahepatic Portal Vein Branches by Clomipramine and Oxethazaine in Isolated Perfused Rat Livers

Abstract

Clomipramine (CLM) and oxethazaine (OXZ) were previously reported to increase portal pressure by contracting portal vein branches (PVBs) in isolated perfused rat liver. In the present study, to characterize the contractile mechanisms, the effects of Y27632, HA1077, staurosporine, papaverine, SKF96365, and sulindac sulfide on the portal pressure increase induced by CLM and OXZ were examined comparatively with those induced by endothelin-1. The results suggest that 1) intrahepatic PVBs employ a Rho-kinase-dependent pathway for sustained contraction, 2) CLM contracts PVBs by activating a Rho-kinase pathway and Ca2+-channels, and 3) OXZ acts primarily by promoting Ca2+ entry through its ionophore-like action. Keywords:: intrahepatic portal vein branch, Rho kinase, clomipramine