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

We investigated which endothelin receptors mediate the vasoconstrictive effects of endothelin-1 on liver circulation.An isolated perfused rat liver model in recirculation was used.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 (p0.01 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.These results indicate that the vasoconstrictive effects of endothelin-1 on the liver circulation are mediated through both ETA and ETB receptors.