The endothelin system in XXXX -7777: an endothelin receptor antagonist inhibits growth in vitro and in vivo.

@entity1 @entity96 @entity2232 @entity5 @entity7283 @entity3 @entity35 @entity157
1. Plasma concentrations of endothelin are increased in @entity1 with @entity96 as well as in @entity1 with liver @entity3 . However, the impact of these findings remains uncertain. 2. We thus analyzed the endothelin system in a @entity35 @entity157 model ( @entity7283 7777) in vitro and in vivo. 3. Our study revealed that tissue concentrations of @entity2232 ( @entity2232 ) and big- @entity2232 , the precursor of @entity2232 , were significantly elevated in @entity7283 7777 as compared to normal liver. The ETA receptor density was significantly elevated, whereas the density of the ETB receptor was @entity7283 7777. 4. We could also demonstrate that @entity157 cells secrete @entity2232 . 5. Exogenously added @entity2232 enhances @entity157 cell growth in a dose-dependent manner. Endothelin receptor antagonists (ETA and combined ETA/ETB receptor antagonists) inhibit @entity5 cell growth in vitro. Since the combined ETA/ETB receptor antagonist was more effective in vitro, we used this compound also for in vivo studies and could demonstrate that a combined ETA/ETB receptor antagonist is able to reduce @entity157 growth in vivo. 6. In conclusion, the endothelin system is activated in @entity7283 7777 and contributes to @entity157 growth. Since endothelin receptor antagonists are well-tolerated upcoming clinically used drugs without major side effects, our data might provide a new pharmacological approach to reduce @entity157 growth in vivo.
