Abstract
Portal hypertension either develops due to progressive liver fibrosis or is the consequence of vascular liver diseases such as portal vein thrombosis or non-cirrhotic portal hypertension. This chapter focuses on different rodent models of liver fibrosis with portal hypertension and also in few non-cirrhotic portal hypertension models. Importantly, after the development of portal hypertension, the proper assessment of drug effects in the portal and systemic circulation should be discussed. The last part of the chapter is dedicated in these techniques to assess the in vivo hemodynamics and the ex vivo techniques of the isolated liver perfusion and vascular contractility.
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References
Trebicka J, Hennenberg M, Laleman W et al (2007) Atorvastatin lowers portal pressure in cirrhotic rats by inhibition of RhoA/Rho-kinase and activation of endothelial nitric oxide synthase. Hepatology 46(1):242–253. doi:10.1002/hep.21673
Trebicka J, Leifeld L, Hennenberg M et al (2008) Hemodynamic effects of urotensin II and its specific receptor antagonist palosuran in cirrhotic rats. Hepatology 47(4):1264–1276. doi:10.1002/hep.22170
Trebicka J, Hennenberg M, Odenthal M et al (2010) Atorvastatin attenuates hepatic fibrosis in rats after bile duct ligation via decreased turnover of hepatic stellate cells. J Hepatol 53(4):702–712. doi:10.1016/j.jhep.2010.04.025
Granzow M, Schierwagen R, Klein S et al (2014) Angiotensin-II type 1 receptor-mediated Janus kinase 2 activation induces liver fibrosis. Hepatology 60(1):334–348. doi:10.1002/hep.27117
Klein S, Herath CB, Schierwagen R et al (2015) Hemodynamic effects of the non-peptidic angiotensin-(1-7) agonist AVE0991 in liver cirrhosis. PLoS One 10(9):e0138732. doi:10.1371/journal.pone.0138732
Klein S, Rick J, Lehmann J et al (2015) Janus-kinase-2 relates directly to portal hypertension and to complications in rodent and human cirrhosis. Gut. doi:10.1136/gutjnl-2015-309600
Schierwagen R, Maybuchen L, Zimmer S et al (2015) Seven weeks of Western diet in apolipoprotein-E-deficient mice induce metabolic syndrome and non-alcoholic steatohepatitis with liver fibrosis. Sci Rep 5:12931. doi:10.1038/srep12931
Uschner FE, Ranabhat G, Choi SS et al (2015) Statins activate the canonical hedgehog-signaling and aggravate non-cirrhotic portal hypertension, but inhibit the non-canonical hedgehog signaling and cirrhotic portal hypertension. Sci Rep 5:14573. doi:10.1038/srep14573
Klein S, Hinuber C, Hittatiya K et al (2016) Novel rat model of repetitive portal venous embolization mimicking human non-cirrhotic idiopathic portal hypertension. PLoS One 11(9):e0162144. doi:10.1371/journal.pone.0162144
Heller J, Trebicka J, Shiozawa T et al (2005) Vascular, hemodynamic and renal effects of low-dose losartan in rats with secondary biliary cirrhosis. Liver Int 25(3):657–666. doi:10.1111/j.1478-3231.2005.01053.x
Hennenberg M, Biecker E, Trebicka J et al (2006) Defective RhoA/Rho-kinase signaling contributes to vascular hypocontractility and vasodilation in cirrhotic rats. Gastroenterology 130(3):838–854. doi:10.1053/j.gastro.2005.11.029
Zhou Q, Hennenberg M, Trebicka J et al (2006) Intrahepatic upregulation of RhoA and Rho-kinase signalling contributes to increased hepatic vascular resistance in rats with secondary biliary cirrhosis. Gut 55(9):1296–1305. doi:10.1136/gut.2005.081059
Hennenberg M, Trebicka J, Biecker E et al (2007) Vascular dysfunction in human and rat cirrhosis: role of receptor-desensitizing and calcium-sensitizing proteins. Hepatology 45(2):495–506. doi:10.1002/hep.21502
Trebicka J, Hennenberg M, Schulze Probsting A et al (2009) Role of beta3-adrenoceptors for intrahepatic resistance and portal hypertension in liver cirrhosis. Hepatology 50(6):1924–1935. doi:10.1002/hep.23222
Acknowledgment
The Laboratory is supported by grants from the Deutsche Forschungsgemeinschaft (SFB TRR57 to P18), the H. J. & W. Hector Stiftung, Ernst-Bertha-Grimmke-Stiftung (6/15) and European Union’s Horizon 2020 research and innovation programme (No 668031).
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Klein, S., Schierwagen, R., Uschner, F.E., Trebicka, J. (2017). Mouse and Rat Models of Induction of Hepatic Fibrosis and Assessment of Portal Hypertension. In: Rittié, L. (eds) Fibrosis. Methods in Molecular Biology, vol 1627. Humana Press, New York, NY. https://doi.org/10.1007/978-1-4939-7113-8_7
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DOI: https://doi.org/10.1007/978-1-4939-7113-8_7
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