Molecular mechanisms of increased intrahepatic resistance in portal hypertension

Portal hypertension is associated with changes in the intrahepatic, systemic, and portosystemic collateral circulation. Alterations in vasoreactivity (vasodilation and vasoconstriction) play a central role in the pathogenesis of portal hypertension by contributing to increased intrahepatic resistance, hyperdynamic circulation, and expansion of the collateral circulation. Portal hypertension is also importantly characterized by changes in vascular structure; termed vascular remodeling, which is an adaptive response of the vessel wall that occurs in response to chronic changes in the environment such as shear stress. These complementary processes of vasoreactivity and vascular remodeling contribute importantly to increased intrahepatic resistance and represent important targets in the treatment of portal hypertension. This review will focus on these processes within the intrahepatic circulation, a circulatory bed whose study, that Dr Roberto Groszmann has pioneered.