Gut, 2013-01, Vol.62 (1), p.138-145
2013
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- Autor(en) / Beteiligte
- Titel
- Increased nitric oxide production in lymphatic endothelial cells causes impairment of lymphatic drainage in cirrhotic rats
- Ist Teil von
- Gut, 2013-01, Vol.62 (1), p.138-145
- Ort / Verlag
- London: BMJ Publishing Group Ltd and British Society of Gastroenterology
- Erscheinungsjahr
- 2013
- Quelle
- BMJ Journals Archiv - DFG Nationallizenzen
- Beschreibungen/Notizen
- Background and aim 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. Methods Cirrhosis was induced in rats by CCl4 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-NG-methyl-L-arginine (L-NMMA) treatment (0.5 mg/kg/day). Results 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 days 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. Conclusions 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.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 0017-5749, 1468-3288eISSN: 1468-3288DOI: 10.1136/gutjnl-2011-300703Titel-ID: cdi_swepub_primary_oai_DiVA_org_uu_192009
- Format
- –
- Schlagworte
- Animals, ascites, Ascites - etiology, Biological and medical sciences, Biomarkers - metabolism, Carbon Tetrachloride, cirrhosis, endothelial cells, Endothelial Cells - metabolism, Endothelium, Lymphatic - metabolism, Endothelium, Lymphatic - pathology, Endothelium, Lymphatic - physiopathology, fibrosis, fluid retention in liver disease, Gastroenterology. Liver. Pancreas. Abdomen, hepatic circulation, hepatic fibrosis, hepatic haemodynamics, hepatic metastases, hepatic stellate cell, hepatitis, Liver cirrhosis, Liver Cirrhosis - chemically induced, Liver Cirrhosis - physiopathology, Liver diseases, Liver. Biliary tract. Portal circulation. Exocrine pancreas, Lymphatic system, Lymphatic System - metabolism, Lymphatic System - pathology, Lymphatic System - physiopathology, lymphatic vessels, Lymphography, Male, Medical sciences, Mortality, Myocytes, Smooth Muscle - pathology, Nitric oxide, Nitric Oxide - metabolism, Nitric Oxide Synthase - antagonists & inhibitors, Nitric Oxide Synthase - metabolism, omega-N-Methylarginine - metabolism, Other diseases. Semiology, Pathogenesis, Plasma, Random Allocation, Rats, Rats, Wistar, Rodents, Smooth muscle, Studies