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“Ribera J, Pauta M, Melgar-Lesmes P, Tugues S, Fernandez-Varo G, Held KF, et al. Increased nitric oxide production in lymphatic endothelial cells causes impairment of lymphatic drainage in cirrhotic rats. Gut 2013;62:138-145. (Reprinted with permission.) The lymphatic network plays a major role in maintaining tissue fluid homoeostasis. However, the role of the lymphatic system in the pathogenesis of ascites and edema formation in cirrhosis has not been fully clarified. high throughput screening assay The aim of this study was to investigate whether the inability of the lymphatic system to drain tissue exudate contributes to the edema observed in cirrhosis. 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). http://www.selleckchem.com/products/Trichostatin-A.html 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). 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. Thus, up regulation of eNOS in

the LyECs tuclazepam of CH rats causes long-term lymphatic remodeling, which is characterized 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. The lymphatic system is a major accessory route, carrying large particulates from interstitial spaces into the blood circulation.[1] The lymph is formed by the result of the net filtration pressure across the capillary basement membrane in the tissues as determined by the Starling forces.[2] The rate of lymph formation, respiration, and skeletal muscle movement primarily determine the lymphatic flow rate.[3] The endothelial cells of the lymphatic collecting duct are covered by smooth muscle cells which contract and act as intrinsic lymphatic pump, hence facilitating lymph flow.[4] When there is an increased interstitial fluid pressure, the overlapping junctions are thrown open and the lymphatic capillaries become hyperpermeable to carry the excess fluid away from interstitium back to circulation.