Molecular mechanisms in the pathogenesis of cirrhotic portal hypertension: focus on nitric oxide

Abstract Portal hypertension occurs because of increased intrahepatic resistance in addition to increased portal venous inflow. Nitric oxide (NO) is a gaseous molecule implicated in several of the vascular derangements that characterize and contribute to portal hypertension and this will be the focus of this review article. In the intrahepatic circulation, NO bioavailability is diminished due to defects in endothelial NO synthase (eNOS) regulation that contribute to increased intrahepatic resistance. NO bioavailability is increased in the splanchnic and systemic circulation because of increased eNOS protein expression and eNOS enzyme activation, which contributes to splanchnic vasodilation and increased portal venous inflow. Therapies to modulate NO bioavailability in portal hypertension are under investigation in humans and animal models.