{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T14:45:17Z","timestamp":1791297917235,"version":"4.1.0"},"reference-count":53,"publisher":"BMJ","issue":"9","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Gut"],"published-print":{"date-parts":[[2006,9]]},"abstract":"<jats:p>\n                    <jats:bold>Background and aims:<\/jats:bold>\n                    Portal hypertension in cirrhosis is mediated in part by increased intrahepatic resistance, reflecting an increased sensitivity of the hepatic microvasculature to vasoconstrictors. Activation of the RhoA\/Rho-kinase pathway is essential for contraction of vascular smooth muscle. The aim of this study was to investigate RhoA\/Rho-kinase mediated regulation of the intrahepatic vascular tone in cirrhotic rats.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>Methods:<\/jats:bold>\n                    Cirrhosis was induced by bile duct ligation (BDL). Hepatic RhoA and Rho-kinase expressions were studied by real time reverse transcription polymerase chain reaction and western blot analysis. Hepatic Rho-kinase activity in rat and human livers was assessed as phosphorylation of the Rho-kinase substrate moesin. The effect of the Rho-kinase inhibitor Y-27632 on hepatic perfusion pressure was measured in livers perfused at constant flow. The in vivo effect of intravenous application of Y-27632 was studied by haemodynamic measurements.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>Results:<\/jats:bold>\n                    Hepatic expressions of RhoA and Rho-kinase were increased at mRNA and protein level in BDL rats. Intrahepatic moesin phosphorylation was increased in livers from cirrhotic rats and patients with alcohol induced cirrhosis. Y-27632 reduced the basal perfusion pressure of in situ perfused livers in BDL rats but not in sham operated rats. Y-27632 reduced the sensitivity to methoxamine in isolated perfused livers in sham operated rats more than in BDL rats. In vivo, Y-27632 reduced portal pressure to a greater extent in BDL rats than in sham operated rats. Intrahepatic vascular resistance was decreased in response to bolus injection of Y-27632 in BDL rats but not in sham operated rats.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>Conclusions:<\/jats:bold>\n                    Upregulation of RhoA and Rho-kinase contributes to increased intrahepatic resistance in cirrhotic rats and to an increased sensitivity of cirrhotic livers to vasoconstrictors.\n                  <\/jats:p>","DOI":"10.1136\/gut.2005.081059","type":"journal-article","created":{"date-parts":[[2006,2,21]],"date-time":"2006-02-21T22:54:06Z","timestamp":1140562446000},"page":"1296-1305","source":"Crossref","is-referenced-by-count":82,"title":["Intrahepatic upregulation of RhoA and Rho-kinase signalling contributes to increased hepatic vascular resistance in rats with secondary biliary 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