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Detail interactions among recruited\/activated leucocytes, hepatic angiogenesis and fibrogenesis, splanchnic blood pooling, decreased hepatic veins to fluctuated splanchnic blood volume (hepatic venous dysregulation), portal hypertensive syndrome and ascites have never explored in cirrhosis. Our study used two anti\u2010<jats:styled-content style=\"fixed-case\">VEGFR<\/jats:styled-content> agents \u2013 brivanib and sorafenib \u2013 to elucidate the relationship between above abnormalities of nonalcoholic steatohepatitis (<jats:styled-content style=\"fixed-case\">NASH<\/jats:styled-content>)\u2010cirrhotic rats.<\/jats:p><\/jats:sec><jats:sec><jats:title>Materials and methods<\/jats:title><jats:p><jats:styled-content style=\"fixed-case\">NASH<\/jats:styled-content>\u2010cirrhotic rats received 2\u2010week brivanib, sorafenib or vehicle (<jats:styled-content style=\"fixed-case\">NASH<\/jats:styled-content>\u2010cirrhotic+briv, <jats:styled-content style=\"fixed-case\">NASH<\/jats:styled-content>\u2010cirrhotic+soraf and <jats:styled-content style=\"fixed-case\">NASH<\/jats:styled-content>\u2010cirrhotic rats) were included for various measurements.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>In comparison with <jats:styled-content style=\"fixed-case\">NASH<\/jats:styled-content>\u2010cirrhotic rats, significant decreased plasma <jats:styled-content style=\"fixed-case\">VEGF<\/jats:styled-content>, fibroblast growth factor, platelet\u2010derived growth factor, hepatic tumour necrosis factor (<jats:styled-content style=\"fixed-case\">TNF<\/jats:styled-content>\u03b1), <jats:styled-content style=\"fixed-case\">IL<\/jats:styled-content>\u20101\u03b2, <jats:styled-content style=\"fixed-case\">IL<\/jats:styled-content>\u20106, <jats:styled-content style=\"fixed-case\">IL<\/jats:styled-content>\u201017 were accompanied by decreased leucocyte mass\/activity (<jats:sup>99\u00a0m<\/jats:sup>Tc\u2010phytate and <jats:sup>18<\/jats:sup>F\u2010<jats:styled-content style=\"fixed-case\">FDG SPECT<\/jats:styled-content>\/<jats:styled-content style=\"fixed-case\">PET<\/jats:styled-content>\/<jats:styled-content style=\"fixed-case\">CT<\/jats:styled-content> scans), hepatic leucocytes recruitment\/microvascular density (fluorescence\u2010enhanced intravital microscopy) and hydroxyproline content, and increased hepatic blood flow in <jats:styled-content style=\"fixed-case\">NASH<\/jats:styled-content>\u2010cirrhotic+briv and <jats:styled-content style=\"fixed-case\">NASH<\/jats:styled-content>\u2010cirrhotic+soraf rats. In addition, increased hepatic microvasculatures compliance\u2010related improved buffering effect of portal vein to acute mannitol infusion was associated with decreased circulating nitric oxide and aldosterone, plasma volume expansion (dye dilution method), splanchnic blood pooling (<jats:sup>99\u00a0m<\/jats:sup>Tc\u2010<jats:styled-content style=\"fixed-case\">RBC SPECT<\/jats:styled-content>\/<jats:styled-content style=\"fixed-case\">PET<\/jats:styled-content>\/<jats:styled-content style=\"fixed-case\">CT<\/jats:styled-content> scans), peripheral hypotension, portal hypertension and ascites in brivanib and sorafenib\u2010treated <jats:styled-content style=\"fixed-case\">NASH<\/jats:styled-content>\u2010cirrhotic rats.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Besides antifibrotic, antiangiogenic and portal hypertensive effects, chronic antagonism of anti\u2010<jats:styled-content style=\"fixed-case\">VEGFR<\/jats:styled-content> with brivanib and sorafenib improves hepatic blood flow, hepatic venous dysregulation, inhibits leucocytes recruitment\/activation, splanchnic blood pooling and ascites formation in <jats:styled-content style=\"fixed-case\">NASH<\/jats:styled-content>\u2010cirrhotic rats. Thus, brivanib and sorafenib might be ideal therapeutic agents in cirrhotic patients suffering from severe haemodynamic disarrangement and ascites.<\/jats:p><\/jats:sec>","DOI":"10.1111\/liv.12299","type":"journal-article","created":{"date-parts":[[2013,8,2]],"date-time":"2013-08-02T14:09:23Z","timestamp":1375452563000},"page":"521-534","source":"Crossref","is-referenced-by-count":23,"title":["Anti\u2010<scp>VEGFR<\/scp> agents ameliorate hepatic venous dysregulation\/microcirculatory dysfunction, splanchnic venous pooling and ascites of <scp>NASH<\/scp>\u2010cirrhotic rat"],"prefix":"10.1111","volume":"34","author":[{"given":"Ying\u2010Ying","family":"Yang","sequence":"first","affiliation":[{"name":"Division of General Medicine Taipei Veterans General Hospital Taipei Taiwan"},{"name":"Department of Medicine National Yang\u2010Ming University School of Medicine Taipei 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