title: The role of nitric oxide in portal hypertensive systemic and portal vascular pathology.
abstract: Hypotension, low systemic vascular resistance and reduced sensitivity to vasoconstrictor are features of hyperdynamic syndrome in portal hypertension (PH) and are pathogenetic factors triggering most serious clinical complications of liver cirrhosis. Nitric oxide (NO) is a powerful vasodilating agent, released from vascular endothelium cell and effecting relaxation of vascular smooth muscle. An increased release of NO has been proposed to play a role in the pathogenesis of vasodilation and vascular hypocontractility associated with PH. In agreement with this hypothesis, the whole-body production of NO has been found to be increased in PH, and the measurement of NOS mRNA expression in different organs suggest that the splanchnic vascular system is a major source of NO release. Consequently, NO could play a role in the development of the splanchnic hyperaemia, collateral circulation and portal hypertensive gastropathy. Furthermore, increased generation of NO in central circulation likely accounts for pulmonary vasorelaxation and cardiac dysfunction found in cirrhosis. By contrast, PH-associated endothelial dysfunction seems to invalidate the capability of intrahepatic and intrarenal vasculature to produce NO. A deficient NO release in these vascular territories might contribute to enhancement of PH and development of the hepatorenal syndrome. Overall NO hyperproduction is either the cause (induction of iNOS) or the consequence (stimulation of ecNOS) of the hyperdynamic syndrome. This incertitude results from the yet undefined significance of mild and transitory activation of the endotoxin-cytokines axis for iNOS induction and contradictory data on specific iNOS and ecNOS activities. A contribution of each isoform of NOS to pathogenesis of the hyperdynamic syndrome probably depends on the model of PH in animal studies and the aetiology or severity of cirrhosis in human studies.
authors.affiliation: Clinical Department of Gastroenterology, Silesian Medical School, Katowice, Poland.
authors.forename: M
authors.initials: M
authors.lastname: Hartleb
authors.forename: P P
authors.initials: PP
authors.lastname: Michielsen
authors.forename: A
authors.initials: A
authors.lastname: Dziurkowska-Marek
mesh_terms: D000818:Animals; D006801:Humans; D006975:Hypertension, Portal / Q000503:physiopathology*; D008102:Liver Circulation; D008103:Liver Cirrhosis / Q000473:pathology / Q000503:physiopathology*; D009569:Nitric Oxide / Q000378:metabolism*; D011168:Portal System / Q000473:pathology
chemical_list: D009569:Nitric Oxide