Altered NO signaling plays a central role in the pathogenesis of portal hypertension and many of its complications. Intrahepatic NO synthesis and downstream signaling are inhibited at multiple levels promoting vasoconstriction and increased intrahepatic resistance. Within the splanchnic and systemic circulation there is excess NO production resulting in vasodilation, decreased systemic vascular resistance and increased portal inflow. The portal circulation attempts to decompress through collateral vessels where NO is involved in promoting vasodilation, vascular remodeling and angiogenesis. Alterations in NO synthesis and function also contribute to other complications of portal hypertension including hepatic encephalopathy, hepatopulmonary syndrome, cirrhotic cardiomyopathy, portal hypertensive gastropathy and the hepatorenal syndrome. Although advances in organ-specific delivery are needed, targeted modulation of NO pathways holds great promise for therapeutics in portal hypertension.
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