{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,2]],"date-time":"2026-05-02T05:28:55Z","timestamp":1777699735594,"version":"3.51.4"},"reference-count":47,"publisher":"BMJ","issue":"3","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Gut"],"published-print":{"date-parts":[[2002,9]]},"abstract":"<jats:p>\n                    <jats:bold>Background:<\/jats:bold>\n                    Portal hypertension in cirrhosis results from enhanced intrahepatic resistance to an augmented inflow. The former is partly due to an imbalance between intrahepatic vasoconstriction and vasodilatation. Enhanced endothelin-1 and decreased activity of hepatic constitutive endothelial nitric oxide synthase (NOS 3) was reported in carbon tetrachloride (CCl\n                    <jats:sub>4<\/jats:sub>\n                    ) cirrhotic rat liver.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>Aims:<\/jats:bold>\n                    To study whether an increase in hepatic NOS 3 could be obtained in the CCl\n                    <jats:sub>4<\/jats:sub>\n                    cirrhotic rat liver by in vivo cDNA transfer and to investigate a possible effect on portal pressure.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>Methods:<\/jats:bold>\n                    Hepatic NOS 3 immunohistochemistry and western blotting were used to measure the amount of NOS 3 protein. Recombinant adenovirus, carrying cDNA encoding human NOS 3, was injected into the portal vein of CCl\n                    <jats:sub>4<\/jats:sub>\n                    cirrhotic rats. Cirrhotic controls received carrier buffer, naked adenovirus, or adenovirus carrying the lac Z gene.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>Results:<\/jats:bold>\n                    NOS 3 immunoreactivity and amount of protein (western blotting) were significantly decreased in CCl\n                    <jats:sub>4<\/jats:sub>\n                    cirrhotic livers. Following cDNA transfer, NOS 3 expression and the amount of protein were partially restored. Portal pressure was 11.4 (1.6) mm Hg in untreated cirrhotic (n=9) and 11.8 (0.6) in lac Z transfected (n=4) cirrhotic rats but was reduced to 7.8 (1.0) mm Hg (n=9) five days after NOS 3 cDNA transfer. No changes were observed in systemic haemodynamics, in liver tests or urinary nitrates, or in NOS 3 expression in lung or kidney, indicating a highly selective transfer.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>Conclusions:<\/jats:bold>\n                    NOS 3 cDNA transfer to cirrhotic rat liver is feasible and the increase in hepatic NOS 3 leads to a marked decrease in portal hypertension without systemic effects. These data indicate a major haemodynamic role of intrahepatic NOS 3 in the pathogenesis of portal hypertension in CCl\n                    <jats:sub>4<\/jats:sub>\n                    cirrhosis.\n                  <\/jats:p>","DOI":"10.1136\/gut.51.3.440","type":"journal-article","created":{"date-parts":[[2002,10,1]],"date-time":"2002-10-01T15:54:10Z","timestamp":1033487650000},"page":"440-445","source":"Crossref","is-referenced-by-count":82,"title":["In vivo gene transfer of endothelial nitric oxide synthase decreases portal pressure in anaesthetised carbon tetrachloride cirrhotic rats"],"prefix":"10.1136","volume":"51","author":[{"given":"M","family":"Van de Casteele","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"A","family":"Omasta","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"S","family":"Janssens","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"T","family":"Roskams","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"V","family":"Desmet","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"F","family":"Nevens","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"J","family":"Fevery","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"239","published-online":{"date-parts":[[2002,9,1]]},"reference":[{"key":"2025112108451996000_51.3.440.1","unstructured":"Genecin P, Groszmann RJ. 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