{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,21]],"date-time":"2026-10-21T04:00:51Z","timestamp":1792555251076,"version":"4.5.0"},"reference-count":33,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2016,5,14]],"date-time":"2016-05-14T00:00:00Z","timestamp":1463184000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001868","name":"National Science Council","doi-asserted-by":"publisher","award":["NSC 98\u20102314\u2010B\u2010075\u2010028"],"award-info":[{"award-number":["NSC 98\u20102314\u2010B\u2010075\u2010028"]}],"id":[{"id":"10.13039\/501100001868","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Eur J Clin Investigation"],"published-print":{"date-parts":[[2016,6]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Angiogenesis plays a pivotal role in splanchnic hyperaemia and portosystemic collateral formation in cirrhosis. Endothelin\u20101 (<jats:styled-content style=\"fixed-case\">ET<\/jats:styled-content>\u20101), an endothelium\u2010derived vasoconstrictor, has also been implicated in the pathogenesis of cirrhosis and portal hypertension.<\/jats:p><\/jats:sec><jats:sec><jats:title>Design<\/jats:title><jats:p>This study aimed to survey the influences of <jats:styled-content style=\"fixed-case\">ET<\/jats:styled-content>\u20101 in cirrhosis\u2010related angiogenesis. Common bile duct ligation was performed on Spraque\u2013Dawley rats to induce cirrhosis. Since the 14th day after the operation, rats randomly received distilled water (<jats:styled-content style=\"fixed-case\">DW<\/jats:styled-content>, control), bosentan [a nonselective <jats:styled-content style=\"fixed-case\">ET<\/jats:styled-content> receptor (<jats:styled-content style=\"fixed-case\">ETR<\/jats:styled-content>) blocker] or ambrisentan (a selective <jats:styled-content style=\"fixed-case\">ET<jats:sub>A<\/jats:sub>R<\/jats:styled-content> blocker) for 4\u00a0weeks. On the 43rd day, portal and systemic haemodynamics, liver biochemistry, portosystemic shunting degree, mesenteric vascular density, <jats:styled-content style=\"fixed-case\">mRNA<\/jats:styled-content> and\/or protein expressions of relevant angiogenic factors were evaluated.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>In cirrhotic rats, bosentan significantly reduced portal pressure. Ambrisentan did not influence haemodynamics and liver biochemistry. Both of them significantly improved the severity of portosystemic collaterals and decreased the mesenteric vascular density. Compared with the <jats:styled-content style=\"fixed-case\">DW<\/jats:styled-content>\u2010treated cirrhotic rats, splenorenal shunt and mesenteric inducible nitric oxide synthase (<jats:styled-content style=\"fixed-case\">iNOS<\/jats:styled-content>), cyclooxygenase 2 (<jats:styled-content style=\"fixed-case\">COX<\/jats:styled-content>2), vascular endothelial growth factor <jats:styled-content style=\"fixed-case\">mRNA<\/jats:styled-content> expressions and mesenteric <jats:styled-content style=\"fixed-case\">iNOS<\/jats:styled-content>,<jats:styled-content style=\"fixed-case\"> COX<\/jats:styled-content>2, <jats:styled-content style=\"fixed-case\">VEGF<\/jats:styled-content>, phospho\u2010<jats:styled-content style=\"fixed-case\">VEGF<\/jats:styled-content> receptor 2, Akt and phospho\u2010Akt protein expressions were down\u2010regulated in both groups.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>In rats with liver cirrhosis, both nonselective and selective <jats:styled-content style=\"fixed-case\">ET<jats:sub>A<\/jats:sub>R<\/jats:styled-content> blockade ameliorate the severity of portosystemic shunting and mesenteric angiogenesis via the down\u2010regulation of <jats:styled-content style=\"fixed-case\">VEGF<\/jats:styled-content> pathway and relevant angiogenic factors. <jats:styled-content style=\"fixed-case\">ET<\/jats:styled-content> receptors may be targeted to control the severity of portosystemic collaterals and associated complications in cirrhosis.<\/jats:p><\/jats:sec>","DOI":"10.1111\/eci.12636","type":"journal-article","created":{"date-parts":[[2016,4,19]],"date-time":"2016-04-19T06:42:43Z","timestamp":1461048163000},"page":"572-580","source":"Crossref","is-referenced-by-count":22,"title":["Endothelin receptor blockers reduce shunting and angiogenesis in cirrhotic rats"],"prefix":"10.1111","volume":"46","author":[{"given":"Shao\u2010Jung","family":"Hsu","sequence":"first","affiliation":[{"name":"Faculty of Medicine 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