{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,9]],"date-time":"2026-03-09T19:25:40Z","timestamp":1773084340201,"version":"3.50.1"},"reference-count":61,"publisher":"Elsevier BV","issue":"3","license":[{"start":{"date-parts":[[2006,8,1]],"date-time":"2006-08-01T00:00:00Z","timestamp":1154390400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Clinics in Liver Disease"],"published-print":{"date-parts":[[2006,8]]},"DOI":"10.1016\/j.cld.2006.08.011","type":"journal-article","created":{"date-parts":[[2007,1,10]],"date-time":"2007-01-10T15:10:36Z","timestamp":1168441836000},"page":"445-457","source":"Crossref","is-referenced-by-count":29,"title":["Molecular and Structural Basis of Portal Hypertension"],"prefix":"10.1016","volume":"10","author":[{"given":"Richard","family":"Moreau","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Didier","family":"Lebrec","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"78","reference":[{"key":"10.1016\/j.cld.2006.08.011_bib1","first-page":"1426","article-title":"Pathophysiology of portal hypertension","volume":"46","author":"Lebrec","year":"1999","journal-title":"Hepatogastroenterology"},{"key":"10.1016\/j.cld.2006.08.011_bib2","series-title":"Clinical gastroenterology: portal hypertension","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1007\/978-1-59259-885-4_3","article-title":"Cell and molecular mechanisms of increased intrahepatic resistance and hemodynamic correlates","author":"Rockey","year":"2005"},{"key":"10.1016\/j.cld.2006.08.011_bib3","series-title":"Clinical gastroenterology: portal hypertension","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1007\/978-1-59259-885-4_2","article-title":"Anatomy and vascular biology of the cells in the portal circulation","author":"Pinzani","year":"2005"},{"key":"10.1016\/j.cld.2006.08.011_bib4","doi-asserted-by":"crossref","unstructured":"Langer DA, Shah VH. Nitric oxide and portal hypertension: interface of vasoreactivity and angiogenesis. J Hepatol 2006;44:209\u201316.","DOI":"10.1016\/j.jhep.2005.10.004"},{"key":"10.1016\/j.cld.2006.08.011_bib5","doi-asserted-by":"crossref","first-page":"478","DOI":"10.1053\/jhep.2002.31432","article-title":"The paradox of nitric oxide in cirrhosis and portal hypertension: too much, not enough","volume":"35","author":"Wiest","year":"2002","journal-title":"Hepatology"},{"key":"10.1016\/j.cld.2006.08.011_bib6","doi-asserted-by":"crossref","first-page":"1359","DOI":"10.1002\/hep.1840200538","article-title":"Hyperdynamic circulation of liver disease forty years later: pathophysiology and clinical consequences","volume":"20","author":"Groszmann","year":"1994","journal-title":"Hepatology"},{"key":"10.1016\/j.cld.2006.08.011_bib7","doi-asserted-by":"crossref","first-page":"98","DOI":"10.1016\/S0168-8278(88)80512-9","article-title":"Abnormal tissue oxygenation in patients with cirrhosis and liver failure","volume":"7","author":"Moreau","year":"1988","journal-title":"J Hepatol"},{"key":"10.1016\/j.cld.2006.08.011_bib8","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1042\/cs0680023","article-title":"Effects of two models of portal hypertension on splanchnic organ blood flow in the rat","volume":"68","author":"Lebrec","year":"1985","journal-title":"Clin Sci"},{"key":"10.1016\/j.cld.2006.08.011_bib9","doi-asserted-by":"crossref","first-page":"370","DOI":"10.1016\/0168-8278(95)80292-4","article-title":"Endogenous factors involved in the control of arterial tone in cirrhosis","volume":"22","author":"Moreau","year":"1995","journal-title":"J Hepatol"},{"key":"10.1016\/j.cld.2006.08.011_bib10","doi-asserted-by":"crossref","first-page":"255","DOI":"10.1016\/S0163-7258(01)00127-9","article-title":"Vascular smooth muscle cell signaling in cirrhosis and portal hypertension","volume":"89","author":"Bomzon","year":"2001","journal-title":"Pharmacol Ther"},{"key":"10.1016\/j.cld.2006.08.011_bib11","series-title":"Clinical gastroenterology: portal hypertension","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1007\/978-1-59259-885-4_4","article-title":"Molecular mechanisms of systemic vasodilation and hyperdynamic circulatory state of cirrhosis","author":"Moreau","year":"2005"},{"key":"10.1016\/j.cld.2006.08.011_bib12","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1016\/S0168-8278(00)80422-5","article-title":"Complications of cirrhosis. I. Portal hypertension","volume":"32","author":"Bosch","year":"2003","journal-title":"J Hepatol"},{"key":"10.1016\/j.cld.2006.08.011_bib13","doi-asserted-by":"crossref","first-page":"886","DOI":"10.1053\/j.gastro.2003.12.012","article-title":"Anti-VEGF receptor-2 monoclonal antibody prevents portal-systemic collateral vessel formation in portal hypertensive mice","volume":"126","author":"Fernandez","year":"2004","journal-title":"Gastroenterology"},{"key":"10.1016\/j.cld.2006.08.011_bib14","doi-asserted-by":"crossref","first-page":"98","DOI":"10.1016\/j.jhep.2005.02.022","article-title":"Inhibition of VEGF receptor-2 decreases the development of hyperdynamic splanchnic circulation and portal-systemic collateral vessels in portal hypertensive rats","volume":"43","author":"Fernandez","year":"2005","journal-title":"J Hepatol"},{"key":"10.1016\/j.cld.2006.08.011_bib15","doi-asserted-by":"crossref","first-page":"639","DOI":"10.1038\/nrm908","article-title":"Seven-transmembrane receptors","volume":"3","author":"Pierce","year":"2002","journal-title":"Nat Rev Mol Cell Biol"},{"key":"10.1016\/j.cld.2006.08.011_bib16","doi-asserted-by":"crossref","first-page":"297","DOI":"10.1038\/379297a0","article-title":"The G-protein nanomachine","volume":"379","author":"Clapham","year":"1996","journal-title":"Nature"},{"key":"10.1016\/j.cld.2006.08.011_bib17","doi-asserted-by":"crossref","first-page":"231","DOI":"10.1038\/372231a0","article-title":"Signal transduction and regulation in smooth muscle","volume":"372","author":"Somlyo","year":"1994","journal-title":"Nature"},{"key":"10.1016\/j.cld.2006.08.011_bib18","doi-asserted-by":"crossref","first-page":"1658","DOI":"10.1096\/fasebj.13.13.1658","article-title":"New insights into the regulation of protein kinase C and novel phorbol ester receptors","volume":"13","author":"Ron","year":"1999","journal-title":"FASEB J"},{"key":"10.1016\/j.cld.2006.08.011_bib19","doi-asserted-by":"crossref","first-page":"806","DOI":"10.1161\/01.RES.78.5.806","article-title":"Identification of protein kinase C isoforms in rat mesenteric small arteries and their possible role in agonist-induced contraction","volume":"78","author":"Ohanian","year":"1996","journal-title":"Circ Res"},{"key":"10.1016\/j.cld.2006.08.011_bib20","doi-asserted-by":"crossref","first-page":"936","DOI":"10.1016\/S0168-8278(01)00090-3","article-title":"Heme oxygenase: protective enzyme or portal hypertensive molecule?","volume":"34","author":"Moreau","year":"2001","journal-title":"J Hepatol"},{"key":"10.1016\/j.cld.2006.08.011_bib21","doi-asserted-by":"crossref","DOI":"10.1053\/j.gastro.2005.11.029","article-title":"Defective RhoA\/Rho-kinase signaling contributes to vascular hypocontractility and vasodilation in cirrhotic rats","author":"Hennenberg","year":"2006","journal-title":"Gastroenterology"},{"key":"10.1016\/j.cld.2006.08.011_bib22","doi-asserted-by":"crossref","first-page":"328","DOI":"10.1096\/fasebj.7.2.7680013","article-title":"Intracellular cyclic GMP receptor proteins","volume":"7","author":"Lincoln","year":"1993","journal-title":"FASEB J"},{"key":"10.1016\/j.cld.2006.08.011_bib23","doi-asserted-by":"crossref","first-page":"1506","DOI":"10.1038\/nm958","article-title":"Regulator of G-protein signaling-2 mediates vascular smooth muscle relaxation and blood pressure","volume":"9","author":"Tang","year":"2003","journal-title":"Nat Med"},{"key":"10.1016\/j.cld.2006.08.011_bib24","doi-asserted-by":"crossref","first-page":"201","DOI":"10.1053\/gast.2000.8522","article-title":"Changes in protein kinase C isoforms in association with vascular hyporeactivity in cirrhotic rat aortas","volume":"119","author":"Tazi","year":"2000","journal-title":"Gastroenterology"},{"key":"10.1016\/j.cld.2006.08.011_bib25","doi-asserted-by":"crossref","first-page":"313","DOI":"10.1042\/CS19990077","article-title":"Relationship between vascular reactivity in vitro and blood flows in rats with cirrhosis","volume":"97","author":"Pateron","year":"1999","journal-title":"Clin Sci"},{"key":"10.1016\/j.cld.2006.08.011_bib26","doi-asserted-by":"crossref","first-page":"387","DOI":"10.1016\/S0016-5085(99)70136-8","article-title":"Altered adrenergic responsiveness of endothelium-denuded hepatic arteries and portal veins in patients with cirrhosis","volume":"116","author":"Heller","year":"1999","journal-title":"Gastroenterology"},{"key":"10.1016\/j.cld.2006.08.011_bib27","doi-asserted-by":"crossref","first-page":"203","DOI":"10.1146\/annurev.pharmtox.41.1.203","article-title":"Novel effects of nitric oxide","volume":"41","author":"Davis","year":"2001","journal-title":"Annu Rev Pharmacol Toxicol"},{"key":"10.1016\/j.cld.2006.08.011_bib28","doi-asserted-by":"crossref","first-page":"857","DOI":"10.1161\/01.RES.79.4.857","article-title":"Sustained increase in aortic endothelial nitric oxide synthase expression in vivo in a model of chronic high blood flow","volume":"79","author":"Nadaud","year":"1996","journal-title":"Circ Res"},{"key":"10.1016\/j.cld.2006.08.011_bib29","first-page":"109","article-title":"Nitric oxide: physiology, pathophysiology, and pharmacology","volume":"43","author":"Moncada","year":"1991","journal-title":"Pharmacol Rev"},{"key":"10.1016\/j.cld.2006.08.011_bib30","doi-asserted-by":"crossref","first-page":"196","DOI":"10.1053\/gast.2000.8554","article-title":"Role of aortic nitric oxide synthase 3 (eNOS) in the systemic vasodilation of portal hypertension","volume":"119","author":"Pateron","year":"2000","journal-title":"Gastroenterology"},{"key":"10.1016\/j.cld.2006.08.011_bib31","doi-asserted-by":"crossref","first-page":"1869","DOI":"10.1053\/gast.2002.33586","article-title":"Role of shear stress in aortic eNOS up-regulation in rats with biliary cirrhosis","volume":"122","author":"Tazi","year":"2002","journal-title":"Gastroenterology"},{"key":"10.1016\/j.cld.2006.08.011_bib32","doi-asserted-by":"crossref","first-page":"1223","DOI":"10.1172\/JCI7458","article-title":"Bacterial translocation in cirrhotic rats stimulates eNOS-derived NO production and impairs mesenteric vascular contractility","volume":"104","author":"Wiest","year":"1999","journal-title":"J Clin Invest"},{"key":"10.1016\/j.cld.2006.08.011_bib33","doi-asserted-by":"crossref","first-page":"749","DOI":"10.1146\/annurev.physiol.64.081501.155952","article-title":"Regulation of endothelial nitric oxide synthase: location, location, location","volume":"64","author":"Shaul","year":"2002","journal-title":"Annu Rev Physiol"},{"key":"10.1016\/j.cld.2006.08.011_bib34","first-page":"R1","article-title":"Molecular mechanisms involved in the regulation of the endothelial nitric oxide synthase","volume":"284","author":"Fleming","year":"2003","journal-title":"Am J Physiol"},{"key":"10.1016\/j.cld.2006.08.011_bib35","doi-asserted-by":"crossref","first-page":"C499","DOI":"10.1152\/ajpcell.00122.2003","article-title":"Flow-dependent regulation of endothelial nitric oxide synthase: role of protein kinases","volume":"285","author":"Boo","year":"2003","journal-title":"Am J Physiol"},{"key":"10.1016\/j.cld.2006.08.011_bib36","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1146\/annurev.physiol.59.1.145","article-title":"Ion channels in vascular endothelium","volume":"59","author":"Nilius","year":"1997","journal-title":"Annu Rev Physiol"},{"key":"10.1016\/j.cld.2006.08.011_bib37","doi-asserted-by":"crossref","first-page":"350","DOI":"10.1016\/S0168-8278(01)00141-6","article-title":"Role of small-conductance Ca2+-dependent K+ channels in in vitro NO-mediated aortic hyporeactivity to \u03b1-adrenergic vasoconstriction in rats with cirrhosis","volume":"35","author":"Barri\u00e8re","year":"2001","journal-title":"J Hepatol"},{"key":"10.1016\/j.cld.2006.08.011_bib38","first-page":"G463","article-title":"Hsp90 regulation of endothelial nitric oxide synthase\u00a0contributes to vascular control in portal hypertension","volume":"277","author":"Shah","year":"1999","journal-title":"Am J Physiol"},{"key":"10.1016\/j.cld.2006.08.011_bib39","doi-asserted-by":"crossref","first-page":"303","DOI":"10.1053\/j.gastro.2005.04.016","article-title":"Norfloxacin reduces aortic NO synthases and proinflammatory cytokine up-regulation in cirrhotic rats: role of Akt signaling","volume":"129","author":"Tazi","year":"2005","journal-title":"Gastroenterology"},{"key":"10.1016\/j.cld.2006.08.011_bib40","doi-asserted-by":"crossref","first-page":"1452","DOI":"10.1016\/j.gastro.2003.07.014","article-title":"Mesenteric vasoconstriction triggers nitric oxide overproduction in the superior mesenteric artery of portal hypertensive rats","volume":"125","author":"Tsai","year":"2003","journal-title":"Gastroenterology"},{"key":"10.1016\/j.cld.2006.08.011_bib41","first-page":"G1043","article-title":"NO overproduction by eNOS precedes hyperdynamic splanchnic circulation in portal hypertensive rats","volume":"276","author":"Wiest","year":"1999","journal-title":"Am J Physiol"},{"key":"10.1016\/j.cld.2006.08.011_bib42","first-page":"H2084","article-title":"Phosphorylation of eNOS initiates excessive NO production in early phases of portal hypertension","volume":"282","author":"Iwakiri","year":"2002","journal-title":"Am J Physiol"},{"key":"10.1016\/j.cld.2006.08.011_bib43","doi-asserted-by":"crossref","first-page":"1500","DOI":"10.1016\/S0016-5085(03)00280-4","article-title":"The role of nitric oxide synthase isoforms in extrahepatic portal hypertension: studies in gene-knockout mice","volume":"124","author":"Theodorakis","year":"2003","journal-title":"Gastroenterology"},{"key":"10.1016\/j.cld.2006.08.011_bib44","first-page":"G1074","article-title":"Mice with targeted deletion of eNOS develop hyperdynamic\u00a0circulation associated with portal hypertension","volume":"283","author":"Iwakiri","year":"2002","journal-title":"Am J Physiol"},{"key":"10.1016\/j.cld.2006.08.011_bib45","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1111\/j.1440-1746.1996.tb00002.x","article-title":"Dose-dependent effects of a nitric oxide biosynthesis inhibitor on hyperdynamic circulation in two models of portal hypertension in conscious rats","volume":"11","author":"Pilette","year":"1996","journal-title":"J Gastroenterol Hepatol"},{"key":"10.1016\/j.cld.2006.08.011_bib46","doi-asserted-by":"crossref","first-page":"514","DOI":"10.1164\/rccm.200201-027OC","article-title":"Prevention of gram-negative translocation reduces the severity of hepatopulmonary syndrome","volume":"166","author":"Rabiller","year":"2002","journal-title":"Am J Respir Crit Care Med"},{"key":"10.1016\/j.cld.2006.08.011_bib47","doi-asserted-by":"crossref","first-page":"208","DOI":"10.1053\/jhep.2003.50038","article-title":"Increased lipopolysaccharide binding protein in cirrhotic patients with marked immune and hemodynamic derangement","volume":"37","author":"Albillos","year":"2003","journal-title":"Hepatology"},{"key":"10.1016\/j.cld.2006.08.011_bib48","first-page":"1616","article-title":"Thalidomide inhibits tumor necrosis factor alpha, decreases nitric oxide synthesis, and ameliorates the hyperdynamic circulatory syndrome in portal-hypertensive rats","volume":"23","author":"Lopez-Talavera","year":"1996","journal-title":"Hepatology"},{"key":"10.1016\/j.cld.2006.08.011_bib49","doi-asserted-by":"crossref","first-page":"906","DOI":"10.1002\/hep.510270403","article-title":"Tumor necrosis factor \u03b1 regulates nitric oxide synthase expression in portal hypertensive gastric mucosa of rats","volume":"27","author":"Ohta","year":"1998","journal-title":"Hepatology"},{"key":"10.1016\/j.cld.2006.08.011_bib50","first-page":"G687","article-title":"Factors mediating the hemodynamic effects of tumor necrosis factor-alpha in portal hypertensive rats","volume":"276","author":"Munoz","year":"1999","journal-title":"Am J Physiol"},{"key":"10.1016\/j.cld.2006.08.011_bib51","doi-asserted-by":"crossref","first-page":"393","DOI":"10.1053\/jhep.2002.30958","article-title":"Activation of eNOS in rat portal hypertensive gastric mucosa is mediated by TNF-alpha via the PI3-kinase-Akt signaling pathway","volume":"35","author":"Kawanaka","year":"2002","journal-title":"Hepatology"},{"key":"10.1016\/j.cld.2006.08.011_bib52","doi-asserted-by":"crossref","first-page":"761","DOI":"10.1016\/0016-5085(95)90449-2","article-title":"Tumor necrosis factor alpha: a major contributor to the hyperdynamic circulation in prehepatic portal-hypertensive rats","volume":"108","author":"Lopez-Talavera","year":"1995","journal-title":"Gastroenterology"},{"key":"10.1016\/j.cld.2006.08.011_bib53","doi-asserted-by":"crossref","first-page":"664","DOI":"10.1172\/JCI119578","article-title":"Tyrosine kinase inhibition ameliorates the hyperdynamic state and decreases nitric oxide production in cirrhotic rats with portal hypertension and ascites","volume":"100","author":"Lopez-Talavera","year":"1997","journal-title":"J Clin Invest"},{"key":"10.1016\/j.cld.2006.08.011_bib54","doi-asserted-by":"crossref","first-page":"1508","DOI":"10.1053\/jhep.2003.09039","article-title":"Bacterial translocation up-regulates GTP-cyclohydrolase I in mesenteric vasculature of cirrhotic rats","volume":"38","author":"Wiest","year":"2003","journal-title":"Hepatology"},{"key":"10.1016\/j.cld.2006.08.011_bib55","first-page":"F1110","article-title":"Neuronal nitric oxide synthase and systemic vasodilation in rats with cirrhosis","volume":"279","author":"Xu","year":"2000","journal-title":"Am J Physiol"},{"key":"10.1016\/j.cld.2006.08.011_bib56","doi-asserted-by":"crossref","first-page":"827","DOI":"10.1038\/89953","article-title":"Endocannabinoids acting at vascular CB1 receptors mediate the vasodilated state in advanced liver cirrhosis","volume":"7","author":"Batkai","year":"2001","journal-title":"Nat Med"},{"key":"10.1016\/j.cld.2006.08.011_bib57","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1053\/gast.2002.30305","article-title":"Endogenous cannabinoids: a new system involved in the homeostasis of arterial pressure in experimental cirrhosis in the rat","volume":"122","author":"Ros","year":"2002","journal-title":"Gastroenterology"},{"key":"10.1016\/j.cld.2006.08.011_bib58","doi-asserted-by":"crossref","first-page":"161","DOI":"10.1124\/pr.54.2.161","article-title":"International Union of Pharmacology. XXVII. Classification of cannabinoid receptors","volume":"54","author":"Howlett","year":"2002","journal-title":"Pharmacol Rev"},{"key":"10.1016\/j.cld.2006.08.011_bib59","doi-asserted-by":"crossref","first-page":"671","DOI":"10.1038\/386671a0","article-title":"Mechanisms of angiogenesis","volume":"386","author":"Risau","year":"1997","journal-title":"Nature"},{"key":"10.1016\/j.cld.2006.08.011_bib60","doi-asserted-by":"crossref","first-page":"653","DOI":"10.1038\/nm0603-653","article-title":"Angiogenesis in health and disease","volume":"9","author":"Carmeliet","year":"2003","journal-title":"Nat Med"},{"key":"10.1016\/j.cld.2006.08.011_bib61","doi-asserted-by":"crossref","first-page":"669","DOI":"10.1038\/nm0603-669","article-title":"The biology of VEGF and its receptors","volume":"9","author":"Ferrara","year":"2003","journal-title":"Nat Med"}],"container-title":["Clinics in Liver Disease"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S1089326106000274?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S1089326106000274?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2019,4,23]],"date-time":"2019-04-23T17:22:47Z","timestamp":1556040167000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S1089326106000274"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2006,8]]},"references-count":61,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2006,8]]}},"alternative-id":["S1089326106000274"],"URL":"https:\/\/doi.org\/10.1016\/j.cld.2006.08.011","relation":{},"ISSN":["1089-3261"],"issn-type":[{"value":"1089-3261","type":"print"}],"subject":[],"published":{"date-parts":[[2006,8]]}}}