title: Current concepts on the role of nitric oxide in portal hypertension.
abstract: Portal hypertension (PHT) is defined as a pathological increase in portal venous pressure and frequently accompanies cirrhosis. Portal pressure can be increased by a rise in portal blood flow, an increase in vascular resistance, or the combination. In cirrhosis, the primary factor leading to PHT is an increase in intra-hepatic resistance to blood flow. Although much of this increase is a mechanical consequence of architectural disturbances, there is a dynamic and reversible component that represents up to a third of the increased vascular resistance in cirrhosis. Many vasoactive substances contribute to the development of PHT. Among these, nitric oxide (NO) is the key mediator that paradoxically regulates the sinusoidal (intra-hepatic) and systemic/splanchnic circulations. NO deficiency in the liver leads to increased intra-hepatic resistance while increased NO in the circulation contributes to the hyperdynamic systemic/splanchnic circulation. NO mediated-angiogenesis also plays a role in splanchnic vasodilation and collateral circulation formation. NO donors reduce PHT in animals models but the key clinical challenge is the development of an NO donor or drug delivery system that selectively targets the liver.
authors.affiliation: Storr Liver Unit, Westmead Millennium Institute and Westmead Hospital, University of Sydney, Westmead, NSW 2145, Australia.
authors.forename: Liang Shuo
authors.initials: LS
authors.lastname: Hu
authors.forename: Jacob
authors.initials: J
authors.lastname: George
authors.forename: Jian Hua
authors.initials: JH
authors.lastname: Wang
mesh_terms: D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology; D006801:Humans; D006975:Hypertension, Portal / Q000188:drug therapy / Q000209:etiology / Q000378:metabolism* / Q000503:physiopathology; D008103:Liver Cirrhosis / Q000150:complications / Q000378:metabolism / Q000503:physiopathology; D009569:Nitric Oxide / Q000378:metabolism*; D020030:Nitric Oxide Donors / Q000494:pharmacology; D019001:Nitric Oxide Synthase / Q000378:metabolism; D017082:Portal Pressure / Q000187:drug effects; D011169:Portal Vein / Q000187:drug effects / Q000378:metabolism* / Q000503:physiopathology; D015398:Signal Transduction; D013152:Splanchnic Circulation
chemical_list: D000959:Antihypertensive Agents; D020030:Nitric Oxide Donors; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase
keywords: Hepatic stellate cell; Liver cirrhosis; Nitric oxide; Portal hypertension
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