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They may improve portal hypertension (PH), but contradictory data on efficacy and side\u2010effects have been reported. Non\u2010selective beta blockers (NSBB) reduce portal pressure, but might aggravate ED. Thus, we evaluated the combination of PDE\u20105\u2010I with NSBB and its impact on PH and ED in experimental cirrhosis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>ED was assessed in cirrhotic patients (n\u00a0=\u00a086) using standardized questionnaire. Experimental cirrhosis was induced by bile\u2010duct\u2010ligation or carbon\u2010tetrachloride intoxication in rats. Corpus cavernosum pressure \u2013 a surrogate of ED \u2010, as well as systemic and portal haemodynamics, were measured in vivo and in situ after acute administration of udenafil alone or in combination with propranolol. mRNA and protein levels of PDE\u20105 signalling were analysed using PCR and western Blot.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>ED in humans was related to severity of liver disease and to NSBB treatment. PDE\u20105 was mainly expressed in hepatic stellate cells and upregulated in human and experimental cirrhosis. Propranolol reduced corpus cavernosum pressure in cirrhotic rats and it was restored by udenafil. Even though udenafil treatment improved PH, it led to a reduction of mean arterial pressure. The combination of udenafil and propranolol reduced portal pressure and hepatic resistance without systemic side\u2010effects.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>ED is common with advanced cirrhosis and concomitant NSBB treatment. The combination of PDE\u20105\u2010I and NSBB improves ED and PH in experimental cirrhosis.<\/jats:p><\/jats:sec>","DOI":"10.1111\/liv.14586","type":"journal-article","created":{"date-parts":[[2020,7,6]],"date-time":"2020-07-06T10:36:30Z","timestamp":1594031790000},"page":"2228-2241","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Combination of phosphodiesterase\u20105\u2010inhibitors and beta blockers improves experimental portal hypertension and erectile dysfunction"],"prefix":"10.1111","volume":"40","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3760-2887","authenticated-orcid":false,"given":"Frank E.","family":"Uschner","sequence":"first","affiliation":[{"name":"Department of Internal Medicine I Hospital of the Goethe University Frankfurt Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kathleen","family":"Gl\u00fcckert","sequence":"additional","affiliation":[{"name":"Department of 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University Frankfurt Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2330-0017","authenticated-orcid":false,"given":"Mattias","family":"Mandorfer","sequence":"additional","affiliation":[{"name":"Hepatic Hemodynamic Lab Medical University Vienna Vienna Austria"},{"name":"Division of Gastroenterology &amp; Hepatology Department of Internal Medicine III Medical University of Vienna Vienna Austria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fernando","family":"Magdaleno","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine I University Hospital Bonn Bonn Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cristina","family":"Ortiz","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine I Hospital of the Goethe University Frankfurt 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