Premium
Combination of phosphodiesterase‐5‐inhibitors and beta blockers improves experimental portal hypertension and erectile dysfunction
Author(s) -
Uschner Frank E.,
Glückert Kathleen,
Paternostro Rafael,
Gnad Thorsten,
Schierwagen Robert,
Mandorfer Mattias,
Magdaleno Fernando,
Ortiz Cristina,
Schwarzkopf Katharina,
Kamath Patrick S.,
Alessandria Carlo,
Boesecke Christoph,
Pfeifer Alexander,
Reiberger Thomas,
Kreisel Wolfgang,
Sauerbruch Tilman,
Ferlitsch Arnulf,
Trebicka Jonel,
Klein Sabine
Publication year - 2020
Publication title -
liver international
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.873
H-Index - 110
eISSN - 1478-3231
pISSN - 1478-3223
DOI - 10.1111/liv.14586
Subject(s) - portal hypertension , cirrhosis , portal venous pressure , medicine , propranolol , erectile dysfunction , gastroenterology , cgmp specific phosphodiesterase type 5 , concomitant
Background & Aims Phosphodiesterase‐5 inhibitors (PDE‐5‐I) are used for treatment of erectile dysfunction (ED), which is common in patients with cirrhosis. They may improve portal hypertension (PH), but contradictory data on efficacy and side‐effects have been reported. Non‐selective beta blockers (NSBB) reduce portal pressure, but might aggravate ED. Thus, we evaluated the combination of PDE‐5‐I with NSBB and its impact on PH and ED in experimental cirrhosis. Methods ED was assessed in cirrhotic patients (n = 86) using standardized questionnaire. Experimental cirrhosis was induced by bile‐duct‐ligation or carbon‐tetrachloride intoxication in rats. Corpus cavernosum pressure – a surrogate of ED ‐, 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‐5 signalling were analysed using PCR and western Blot. Results ED in humans was related to severity of liver disease and to NSBB treatment. PDE‐5 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‐effects. Conclusions ED is common with advanced cirrhosis and concomitant NSBB treatment. The combination of PDE‐5‐I and NSBB improves ED and PH in experimental cirrhosis.