{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,4]],"date-time":"2026-04-04T04:31:50Z","timestamp":1775277110829,"version":"3.50.1"},"reference-count":26,"publisher":"BMJ","issue":"1","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Gut"],"accepted":{"date-parts":[[2011,12,21]]},"published-print":{"date-parts":[[2013,1]]},"abstract":"<jats:sec>\n                    <jats:title>Background and aim<\/jats:title>\n                    <jats:p>The lymphatic network plays a major role in maintaining tissue fluid homoeostasis. Therefore several pathological conditions associated with oedema formation result in deficient lymphatic function. However, the role of the lymphatic system in the pathogenesis of ascites and oedema formation in cirrhosis has not been fully clarified. The aim of this study was to investigate whether the inability of the lymphatic system to drain tissue exudate contributes to the oedema observed in cirrhosis.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Cirrhosis was induced in rats by CCl\n                      <jats:sub>4<\/jats:sub>\n                      inhalation. Lymphatic drainage was evaluated using fluorescent lymphangiography. Expression of endothelial nitric oxide synthase (eNOS) was measured in primary lymphatic endothelial cells (LyECs). Inhibition of eNOS activity in cirrhotic rats with ascites (CH) was carried out by L-N\n                      <jats:sup>G<\/jats:sup>\n                      -methyl-L-arginine (L-NMMA) treatment (0.5\u2005mg\/kg\/day).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>The (CH) rats had impaired lymphatic drainage in the splanchnic and peripheral regions compared with the control (CT) rats. LyECs isolated from the CH rats showed a significant increase in eNOS and nitric oxide (NO) production. In addition, the lymphatic vessels of the CH rats showed a significant reduction in smooth muscle cell (SMC) coverage compared with the CT rats. CH rats treated with L-NMMA for 7\u2005days showed a significant improvement in lymphatic drainage and a significant reduction in ascites volume, which were associated with increased plasma volume. This beneficial effect of L-NMMA inhibition was also associated with a significant increase in lymphatic SMC coverage.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>The upregulation of eNOS in the LyECs of CH rats causes long-term lymphatic remodelling, which is characterised by a loss of SMC lymphatic coverage. The amelioration of this lymphatic abnormality by chronic eNOS inhibition results in improved lymphatic drainage and reduced ascites.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1136\/gutjnl-2011-300703","type":"journal-article","created":{"date-parts":[[2012,1,21]],"date-time":"2012-01-21T01:42:39Z","timestamp":1327110159000},"page":"138-145","source":"Crossref","is-referenced-by-count":53,"title":["Increased nitric oxide production in lymphatic endothelial cells causes impairment of lymphatic drainage in cirrhotic rats"],"prefix":"10.1136","volume":"62","author":[{"given":"Jordi","family":"Ribera","sequence":"first","affiliation":[{"name":"Department of Biochemistry and Molecular Genetics, Hospital Clinic of Barcelona, IDIBAPS, CIBERehd, Barcelona, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Montse","family":"Pauta","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Genetics, Hospital Clinic of Barcelona, IDIBAPS, CIBERehd, Barcelona, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pedro","family":"Melgar-Lesmes","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Genetics, Hospital Clinic of Barcelona, IDIBAPS, CIBERehd, Barcelona, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"S\u00f2nia","family":"Tugues","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Genetics, Hospital Clinic of Barcelona, IDIBAPS, CIBERehd, Barcelona, Spain"},{"name":"Department of Immunology, Genetics and Pathology, Rudbecklaboratoriet, Uppsala, Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Guillermo","family":"Fern\u00e1ndez-Varo","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Genetics, Hospital Clinic of Barcelona, IDIBAPS, CIBERehd, Barcelona, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kara F","family":"Held","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Vascular Biology and Therapeutics Program, Yale University, New Haven, Connecticut, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Guadalupe","family":"Soria","sequence":"additional","affiliation":[{"name":"Experimental 7T-MRI Unit, IDIBAPS, Barcelona, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ra\u00fal","family":"Tudela","sequence":"additional","affiliation":[{"name":"Experimental 7T-MRI Unit, IDIBAPS, Barcelona, Spain"},{"name":"CIBER-BBN, Group of Biomedical Imaging of the University of Barcelona, Barcelona, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anna M","family":"Planas","sequence":"additional","affiliation":[{"name":"Experimental 7T-MRI Unit, IDIBAPS, Barcelona, Spain"},{"name":"Department of Brain Ischemia and Neurodegeneration, IIBB-CSIC, IDIBAPS, Barcelona, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Carlos","family":"Fern\u00e1ndez-Hernando","sequence":"additional","affiliation":[{"name":"Departments of Medicine and Cell Biology, Leon H. Charney Division of Cardiology and the Marc and Ruti Bell Vascular Biology and Disease Program, New York University School of Medicine, New York, NY, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vicente","family":"Arroyo","sequence":"additional","affiliation":[{"name":"Liver Unit-Institut de Malalties Digestives, Hospital Cl\u00ednic i Provincial de Barcelona, IDIBAPS, CIBERehd, University of Barcelona, Barcelona, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wladimiro","family":"Jim\u00e9nez","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Genetics, Hospital Clinic of Barcelona, IDIBAPS, CIBERehd, Barcelona, Spain"},{"name":"Department of Physiological Sciences I, University of Barcelona, Barcelona, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Manuel","family":"Morales-Ruiz","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Genetics, Hospital Clinic of Barcelona, IDIBAPS, CIBERehd, Barcelona, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"239","published-online":{"date-parts":[[2012,1,20]]},"reference":[{"key":"2025120618201364000_62.1.138.1","doi-asserted-by":"crossref","first-page":"258","DOI":"10.1053\/jhep.2003.50315","article-title":"The management of ascites in cirrhosis: report on the consensus conference of the International Ascites Club","volume":"38","author":"Moore","year":"2003","journal-title":"Hepatology"},{"key":"2025120618201364000_62.1.138.2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra035021"},{"key":"2025120618201364000_62.1.138.3","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2009.08.068"},{"key":"2025120618201364000_62.1.138.4","doi-asserted-by":"crossref","unstructured":"Henriksen JH Moller S . 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