title: The molecules: mechanisms of arterial vasodilatation observed in the splanchnic and systemic circulation in portal hypertension.
abstract: A hyperdynamic splanchnic and systemic circulation is typical of cirrhotic patients and has been observed in all experimental forms of portal hypertension. The hyperdynamic circulation is most likely initiated by arterial vasodilatation, leading to central hypovolemia, sodium retention, and an increased intravascular volume. Arterial vasodilatation is regulated by a complex interplay of various vasodilator molecules and factors that influence the production of those vasodilator molecules. Nitric oxide (NO) has been recognized as the most important vasodilator molecule that mediates the excessive arterial vasodilatation observed in portal hypertension. The aims of this review are (1) to categorize NO synthase isoforms involved in NO overproduction; (2) to explain the mechanisms of endothelial NO synthase up-regulation; and (3) to summarize other molecules involved in the arterial vasodilatation.
authors.affiliation: Section of Digestive Diseases, Department of Internal Medicine, Yale University School of Medicine, New Haven, CT 06520, USA. yasuko.iwakiri@yale.edu
authors.forename: Yasuko
authors.initials: Y
authors.lastname: Iwakiri
mesh_terms: D053607:Adrenomedullin / Q000378:metabolism; D000818:Animals; D001158:Arteries / Q000378:metabolism / Q000503:physiopathology; D001685:Biological Factors / Q000378:metabolism; D063385:Cannabinoid Receptor Modulators / Q000378:metabolism; D002248:Carbon Monoxide / Q000378:metabolism; D003067:Coenzymes / Q000378:metabolism; D004730:Endothelium, Vascular / Q000201:enzymology / Q000378:metabolism* / Q000503:physiopathology; D011464:Epoprostenol / Q000378:metabolism; D006801:Humans; D006862:Hydrogen Sulfide / Q000378:metabolism; D006975:Hypertension, Portal / Q000209:etiology / Q000378:metabolism* / Q000503:physiopathology; D008103:Liver Cirrhosis / Q000150:complications* / Q000378:metabolism / Q000503:physiopathology; D009569:Nitric Oxide / Q000378:metabolism*; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism*; D017082:Portal Pressure; D013152:Splanchnic Circulation; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D015854:Up-Regulation; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism; D014664:Vasodilation; D014665:Vasodilator Agents / Q000378:metabolism*
chemical_list: D001685:Biological Factors; D063385:Cannabinoid Receptor Modulators; D003067:Coenzymes; D014409:Tumor Necrosis Factor-alpha; D042461:Vascular Endothelial Growth Factor A; D014665:Vasodilator Agents; C067410:endothelium-dependent hyperpolarization factor; D053607:Adrenomedullin; D009569:Nitric Oxide; D002248:Carbon Monoxide; D011464:Epoprostenol; D052250:Nitric Oxide Synthase Type III; D006862:Hydrogen Sulfide