{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,2]],"date-time":"2026-05-02T05:25:48Z","timestamp":1777699548587,"version":"3.51.4"},"reference-count":47,"publisher":"BMJ","issue":"1","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Gut"],"published-print":{"date-parts":[[2009,1]]},"abstract":"\n Background:<\/jats:title>\n \n Increased intrahepatic vascular tone in cirrhosis has been attributed to a decrease of hepatic nitric oxide (NO) secondary to disturbances in the post-translational regulation of the enzyme eNOS. NO scavenging by superoxide (O\n 2<\/jats:sub>\n \u2212<\/jats:sup>\n ) further contributes to a reduction of NO bioavailability in cirrhotic livers.\n <\/jats:p>\n <\/jats:sec>\n \n Aim:<\/jats:title>\n \n To investigate whether removing increased O\n 2<\/jats:sub>\n \u2212<\/jats:sup>\n levels could be a new therapeutic strategy to increase intrahepatic NO, improve endothelial dysfunction and reduce portal pressure in cirrhotic rats with portal hypertension.\n <\/jats:p>\n <\/jats:sec>\n \n Methods:<\/jats:title>\n \n Adenoviral vectors expressing extracellular superoxide dismutase (SOD) (AdECSOD) or \u03b2-galactosidase (Ad\u03b2gal) were injected intravenously in control and CCl\n 4<\/jats:sub>\n -induced cirrhotic rats. After 3 days, liver O\n 2<\/jats:sub>\n \u2212<\/jats:sup>\n levels were determined by dihydroethidium staining, NO bioavailability by hepatic cGMP levels, nitrotyrosinated proteins by immunohistochemistry and western blot, and endothelial function by responses to acetylcholine in perfused rat livers. Mean arterial pressure (MAP) and portal pressure were evaluated in vivo.\n <\/jats:p>\n <\/jats:sec>\n \n Results:<\/jats:title>\n \n Transfection of cirrhotic livers with AdECSOD produced a significant reduction in O\n 2<\/jats:sub>\n \u2212<\/jats:sup>\n levels, a significant increase in hepatic cGMP, and a decrease in liver nitrotyrosinated proteins which were associated with a significant improvement in the endothelium-dependent vasodilatation to acetylcholine. In addition, in cirrhotic livers AdECSOD transfection produced a significant reduction in portal pressure (17.3 (SD 2) mm Hg vs 15 (SD 1.6) mm Hg; p<0.05) without significant changes in MAP. In control rats, AdECSOD transfection prevents the increase in portal perfusion pressure promoted by an ROS-generating system.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusions:<\/jats:title>\n \n In cirrhotic rats, reduction of O\n 2<\/jats:sub>\n \u2212<\/jats:sup>\n by AdECSOD increases NO bioavailability, improves intrahepatic endothelial function and reduces portal pressure. These findings suggest that scavenging of O\n 2<\/jats:sub>\n \u2212<\/jats:sup>\n might be a new therapeutic strategy in the management of portal hypertension.\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1136\/gut.2008.149880","type":"journal-article","created":{"date-parts":[[2008,10,1]],"date-time":"2008-10-01T21:22:06Z","timestamp":1222896126000},"page":"118-125","source":"Crossref","is-referenced-by-count":66,"title":["Superoxide dismutase gene transfer reduces portal pressure in CCl\n 4<\/sub>\n cirrhotic rats with portal hypertension"],"prefix":"10.1136","volume":"58","author":[{"given":"B","family":"Lavi\u00f1a","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"J","family":"Gracia-Sancho","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"A","family":"Rodr\u00edguez-Vilarrupla","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Y","family":"Chu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"D D","family":"Heistad","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"J","family":"Bosch","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"J C","family":"Garc\u00eda-Pag\u00e1n","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"239","published-online":{"date-parts":[[2008,10,1]]},"reference":[{"key":"2025112109260200000_58.1.118.1","doi-asserted-by":"crossref","unstructured":"Bosch J Garcia-Pagan JC . Complications of cirrhosis. I. Portal hypertension. J Hepatol 2000;32(1 Suppl):141\u00e2\u0080\u009356.","DOI":"10.1016\/S0168-8278(00)80422-5"},{"key":"2025112109260200000_58.1.118.2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2007.03.014"},{"key":"2025112109260200000_58.1.118.3","doi-asserted-by":"publisher","DOI":"10.1152\/ajpgi.00452.2002"},{"key":"2025112109260200000_58.1.118.4","doi-asserted-by":"publisher","DOI":"10.1002\/hep.510280405"},{"key":"2025112109260200000_58.1.118.5","doi-asserted-by":"publisher","DOI":"10.1016\/S0016-5085(98)70487-1"},{"key":"2025112109260200000_58.1.118.6","doi-asserted-by":"publisher","DOI":"10.1002\/hep.21228"},{"key":"2025112109260200000_58.1.118.7","doi-asserted-by":"publisher","DOI":"10.1016\/S0016-5085(99)70408-7"},{"key":"2025112109260200000_58.1.118.8","doi-asserted-by":"publisher","DOI":"10.1002\/hep.22166"},{"key":"2025112109260200000_58.1.118.9","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2006.11.008"},{"key":"2025112109260200000_58.1.118.10","doi-asserted-by":"publisher","DOI":"10.1186\/1476-5926-2-2"},{"key":"2025112109260200000_58.1.118.11","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.103.14.1893"},{"key":"2025112109260200000_58.1.118.12","doi-asserted-by":"publisher","DOI":"10.1097\/01.TP.0000065299.29900.17"},{"key":"2025112109260200000_58.1.118.13","doi-asserted-by":"publisher","DOI":"10.1038\/sj.gt.3301633"},{"key":"2025112109260200000_58.1.118.14","doi-asserted-by":"publisher","DOI":"10.1161\/01.RES.0000057755.02845.F9"},{"key":"2025112109260200000_58.1.118.15","doi-asserted-by":"crossref","first-page":"2516","DOI":"10.1152\/ajpheart.2001.280.6.H2516","article-title":"Gene transfer of superoxide dismutase isoforms reverses endothelial dysfunction in diabetic rabbit aorta.","volume":"280","author":"Zanetti","year":"2001","journal-title":"Am J Physiol Heart Circ Physiol"},{"key":"2025112109260200000_58.1.118.16","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.00676.2005"},{"key":"2025112109260200000_58.1.118.17","doi-asserted-by":"publisher","DOI":"10.1053\/gast.2002.31040"},{"key":"2025112109260200000_58.1.118.18","doi-asserted-by":"publisher","DOI":"10.1016\/S1046-2023(02)00083-X"},{"key":"2025112109260200000_58.1.118.19","doi-asserted-by":"crossref","first-page":"199","DOI":"10.1136\/gut.45.2.199","article-title":"Reduced oxidative and nitrosative damage in murine experimental colitis in the absence of inducible nitric oxide synthase.","volume":"45","author":"Zingarelli","year":"1999","journal-title":"Gut"},{"key":"2025112109260200000_58.1.118.20","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2007.01.020"},{"key":"2025112109260200000_58.1.118.21","doi-asserted-by":"publisher","DOI":"10.1080\/10715760701297354"},{"key":"2025112109260200000_58.1.118.22","doi-asserted-by":"publisher","DOI":"10.1016\/S0168-8278(03)00347-7"},{"key":"2025112109260200000_58.1.118.23","doi-asserted-by":"crossref","unstructured":"Hernandez-Guerra M Garcia-Pagan JC Bosch J . Increased hepatic resistance: a new target in the pharmacologic therapy of portal hypertension. J Clin Gastroenterol 2005;39(4 Suppl 2):S131\u00e2\u0080\u00937.","DOI":"10.1097\/01.mcg.0000155513.17715.f7"},{"key":"2025112109260200000_58.1.118.24","doi-asserted-by":"crossref","unstructured":"Mittal MK Gupta TK Lee FY .Nitric oxide modulates hepatic vascular tone in normal rat liver. Am J Physiol 1994;267(3 Pt 1):G416\u00e2\u0080\u009322.","DOI":"10.1152\/ajpgi.1994.267.3.G416"},{"key":"2025112109260200000_58.1.118.25","doi-asserted-by":"publisher","DOI":"10.1016\/S0016-5085(00)70368-4"},{"key":"2025112109260200000_58.1.118.26","doi-asserted-by":"publisher","DOI":"10.1002\/hep.510240137"},{"key":"2025112109260200000_58.1.118.27","doi-asserted-by":"publisher","DOI":"10.1053\/gast.2000.17831"},{"key":"2025112109260200000_58.1.118.28","doi-asserted-by":"publisher","DOI":"10.1053\/jhep.2003.50004"},{"key":"2025112109260200000_58.1.118.29","doi-asserted-by":"publisher","DOI":"10.1016\/S0168-8278(04)00137-0"},{"key":"2025112109260200000_58.1.118.30","doi-asserted-by":"publisher","DOI":"10.1136\/gut.51.3.440"},{"key":"2025112109260200000_58.1.118.31","doi-asserted-by":"crossref","first-page":"G1023","DOI":"10.1152\/ajpgi.2000.279.5.G1023","article-title":"Gene transfer of recombinant endothelial nitric oxide synthase to liver in vivo and in vitro.","volume":"279","author":"Shah","year":"2000","journal-title":"Am J Physiol Gastrointest Liver Physiol"},{"key":"2025112109260200000_58.1.118.32","doi-asserted-by":"crossref","first-page":"741","DOI":"10.1172\/JCI7997","article-title":"Gene transfer of the neuronal NO synthase isoform to cirrhotic rat liver ameliorates portal hypertension.","volume":"105","author":"Yu","year":"2000","journal-title":"J Clin Invest"},{"key":"2025112109260200000_58.1.118.33","doi-asserted-by":"publisher","DOI":"10.1016\/S0016-5085(03)00909-0"},{"key":"2025112109260200000_58.1.118.34","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.151136298"},{"key":"2025112109260200000_58.1.118.35","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2003.09.018"},{"key":"2025112109260200000_58.1.118.36","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2003.12.007"},{"key":"2025112109260200000_58.1.118.37","doi-asserted-by":"publisher","DOI":"10.1038\/sj.gt.3300885"},{"key":"2025112109260200000_58.1.118.38","doi-asserted-by":"publisher","DOI":"10.1016\/S1054-3589(08)60964-3"},{"key":"2025112109260200000_58.1.118.39","unstructured":"Kmiec Z . Cooperation of liver cells in health and disease. Adv Anat Embryol Cell Biol 2001;161:III\u00e2\u0080\u0093XIII, 1\u00e2\u0080\u0093151."},{"key":"2025112109260200000_58.1.118.40","doi-asserted-by":"publisher","DOI":"10.1038\/sj.bjp.0702200"},{"key":"2025112109260200000_58.1.118.41","doi-asserted-by":"crossref","first-page":"3945","DOI":"10.1016\/S0021-9258(18)51810-X","article-title":"Studies on rat liver catalase. i. combined immunochemical and enzymatic determination of catalase in liver cell fractions.","volume":"238","author":"Higashi","year":"1963","journal-title":"J Biol Chem"},{"key":"2025112109260200000_58.1.118.42","doi-asserted-by":"publisher","DOI":"10.1016\/S0168-8278(99)80228-1"},{"key":"2025112109260200000_58.1.118.43","doi-asserted-by":"publisher","DOI":"10.1006\/jsre.1995.1168"},{"key":"2025112109260200000_58.1.118.44","doi-asserted-by":"publisher","DOI":"10.1152\/ajpgi.00512.2000"},{"key":"2025112109260200000_58.1.118.45","doi-asserted-by":"publisher","DOI":"10.1016\/S0168-8278(99)80013-0"},{"key":"2025112109260200000_58.1.118.46","doi-asserted-by":"publisher","DOI":"10.1038\/sj.gt.3301647"},{"key":"2025112109260200000_58.1.118.47","doi-asserted-by":"publisher","DOI":"10.1002\/hep.1840100610"}],"container-title":["Gut"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1136\/gut.2008.149880","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,11,21]],"date-time":"2025-11-21T17:26:14Z","timestamp":1763745974000},"score":1,"resource":{"primary":{"URL":"https:\/\/gut.bmj.com\/lookup\/doi\/10.1136\/gut.2008.149880"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2008,10,1]]},"references-count":47,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2008,12,17]]},"published-print":{"date-parts":[[2009,1]]}},"alternative-id":["10.1136\/gut.2008.149880"],"URL":"https:\/\/doi.org\/10.1136\/gut.2008.149880","relation":{},"ISSN":["0017-5749","1468-3288"],"issn-type":[{"value":"0017-5749","type":"print"},{"value":"1468-3288","type":"electronic"}],"subject":[],"published":{"date-parts":[[2008,10,1]]}}}