Endothelin-1 induces liver vasoconstriction through both ETA and ETB receptors

Background/Aims: We investigated which endothelin receptors mediate the vasoconstrictive effects of endothelin-1 on liver circulation. Methods: An isolated perfused rat liver model in recirculation was used. Results: The perfusion of 10−10 M endothelin-1 had no significant influence on the liver flow, whereas 10−9 M endothelin-1 induced significant vasoconstriction, with flow dropping from 3.20±0.34 to 1.48±0.28 ml • min−1 • g−1 liver tissue (p<0.01 vs controls). The liver flow was interrupted following the perfusion of 10−8 M endothelin-1. Sarafatoxin C and BQ 3020, two agonists of ETB receptor, had vasoconstrictive effects in this model. Sarafatoxin C decreased the liver flow in a dose-dependent manner, from 3.32±0.21 to 2.18±0.20, 1.60±0.09, and 1.01±0.06 ml • min−1 • g−1, respectively, with 10−9 M, 10−8 M, and 10−7 M. While BQ 123, an antagonist of ETA receptor, or BQ 788, an antagonist of ETB receptor, partially reversed the effect of 10−9 M endothelin-1, the simultaneous administration of BQ 123 and BQ 788 completely reversed these effects. Conclusions: These results indicate that the vasoconstrictive effects of endothelin-1 on the liver circulation are mediated through both ETA and ETB receptors.