{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,27]],"date-time":"2026-08-27T10:57:27Z","timestamp":1787828247072,"version":"build-2784847793"},"reference-count":39,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2014,1,15]],"date-time":"2014-01-15T00:00:00Z","timestamp":1389744000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"Ministerio de Educaci\u00f3n y Ciencia","award":["SAF 07\/61298"],"award-info":[{"award-number":["SAF 07\/61298"]}]},{"name":"Fondos FEDER"},{"DOI":"10.13039\/501100004587","name":"Instituto de Salud Carlos III","doi-asserted-by":"crossref","award":["BF 538\/07"],"award-info":[{"award-number":["BF 538\/07"]}],"id":[{"id":"10.13039\/501100004587","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Programa de Intensificaci\u00f3n de Actividad Investigadora","award":["INT07\/173"],"award-info":[{"award-number":["INT07\/173"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Liver International"],"published-print":{"date-parts":[[2014,7]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background &amp; Aims<\/jats:title><jats:p>Gap junctions are formed by connexins (<jats:styled-content style=\"fixed-case\">Cx<\/jats:styled-content>), a family of proteins that couple endothelial and smooth muscle cells in systemic vessels. In this context, <jats:styled-content style=\"fixed-case\">Cx<\/jats:styled-content> allow the transmission of signals modulating vascular tone. Recently, vascular <jats:styled-content style=\"fixed-case\">Cx<\/jats:styled-content> have been observed in liver cells implicated in liver blood flow regulation. Here, we investigated the role of <jats:styled-content style=\"fixed-case\">Cx<\/jats:styled-content> in the regulation of intrahepatic vascular tone in cirrhosis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Livers of Sprague\u2013Dawley control and cirrhotic (common bile duct ligation\u2010<jats:styled-content style=\"fixed-case\">CBDL<\/jats:styled-content> and <jats:styled-content style=\"fixed-case\">CC<\/jats:styled-content>l<jats:sub>4<\/jats:sub>) rats were perfused, and concentration\u2013effect curves in response to acetylcholine (<jats:styled-content style=\"fixed-case\">AC<\/jats:styled-content>h) precontracted with methoxamine were obtained in the presence of the specific <jats:styled-content style=\"fixed-case\">Cx<\/jats:styled-content> inhibitor 18\u2010alpha\u2010glycyrrhetinic acid or vehicle. <jats:styled-content style=\"fixed-case\">Cx<\/jats:styled-content> expression was assessed by immunofluorescence, western blot and reverse\u2010transcription polymerase chain reaction in liver tissue, hepatic stellate cells, sinusoidal endothelial cells and hepatocytes isolated from control and cirrhotic rat livers. <jats:styled-content style=\"fixed-case\">Cx<\/jats:styled-content> protein expression was also determined in cirrhotic human tissue.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Gap junction blockade markedly attenuated relaxation of hepatic vasculature in response to <jats:styled-content style=\"fixed-case\">AC<\/jats:styled-content>h in control (maximal relaxation, \u221255\u00a0\u00b1\u00a010.5% vs. \u221295.3\u00a0\u00b1\u00a010% with vehicle; <jats:italic>P\u00a0<\/jats:italic>&lt;<jats:italic>\u00a0<\/jats:italic>0.01) and <jats:styled-content style=\"fixed-case\">CBDL<\/jats:styled-content> rats (50.9\u00a0\u00b1\u00a018.5% vs. \u221218.7\u00a0\u00b1\u00a05.5% with vehicle; <jats:italic>P\u00a0<\/jats:italic>=<jats:italic>\u00a0<\/jats:italic>0.01). Livers from <jats:styled-content style=\"fixed-case\">CBDL<\/jats:styled-content> rats and patients with cirrhosis exhibited <jats:styled-content style=\"fixed-case\">Cx<\/jats:styled-content> overexpression. By contrast, CCl<jats:sub>4<\/jats:sub>\u2010cirrhotic rats did not show attenuated relaxation of hepatic vasculature after blockade and <jats:styled-content style=\"fixed-case\">Cx<\/jats:styled-content> expression was significantly lower than in controls.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Gap junctions may contribute to modulating portal pressure and intrahepatic vascular relaxation. Liver gap junctions may represent a new therapeutic target in cirrhotic portal hypertension.<\/jats:p><\/jats:sec>","DOI":"10.1111\/liv.12446","type":"journal-article","created":{"date-parts":[[2013,12,18]],"date-time":"2013-12-18T15:28:40Z","timestamp":1387380520000},"page":"859-868","source":"Crossref","is-referenced-by-count":21,"title":["Role of gap junctions modulating hepatic vascular tone in cirrhosis"],"prefix":"10.1111","volume":"34","author":[{"given":"Manuel","family":"Hern\u00e1ndez\u2010Guerra","sequence":"first","affiliation":[{"name":"Liver Unit University Hospital of the Canary Islands Tenerife Spain"},{"name":"Department of Internal Medicine University of La Laguna Tenerife Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanira","family":"Gonz\u00e1lez\u2010M\u00e9ndez","sequence":"additional","affiliation":[{"name":"Liver Unit University Hospital of the Canary Islands Tenerife Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zaida A.","family":"de Ganzo","sequence":"additional","affiliation":[{"name":"Liver Unit University Hospital of the Canary Islands Tenerife Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eduardo","family":"Salido","sequence":"additional","affiliation":[{"name":"Department of Pathology University Hospital of the Canary Islands Tenerife Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juan C.","family":"Garc\u00eda\u2010Pag\u00e1n","sequence":"additional","affiliation":[{"name":"Barcelona Hepatic Hemodynamic Laboratory Liver Unit Hospital Clinic IDIBAPS and CIBERehd Barcelona Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Beatriz","family":"Abrante","sequence":"additional","affiliation":[{"name":"Liver Unit University Hospital of the Canary Islands Tenerife Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonio 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