ENDOTHELIN-1 INDUCES LIVER VASOCONSTRICTION THROUGH BOTH ETA AND ETB RECEPTORS

Background/Aims: We investigated which endothelin receptors mediate th e vasoconstrictive effects of endothelin-1 on liver circulation. Metho ds: An isolated perfused rat liver model in recirculation was used. Re sults: The perfusion of 10(-10) M endothelin-1 had no significant infl uence on the liver flow, whereas 10(-9) M endothelin-1 induced signifi cant 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. Sar afatoxin C and BQ 3020, two agonists of ETB receptor, had vasoconstric tive 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 7 88, an antagonist of ETB receptor, partially reversed the effect: of 1 0(-9) M endothelin-1, the simultaneous administration of BQ 123 and BQ 788 completely reversed these effects. Conclusions: These results ind icate that the vasoconstrictive effects of endothelin-1 on the liver c irculation are mediated through both ETA and ETB receptors.