ENDOTHELIN-1 SELECTIVELY CONTRACTS PORTAL-VEIN THROUGH BOTH ETA AND ETA-RECEPTORS IN ISOLATED RABBIT LIVER

We determined the constrictive effects of endothelin (ET)-1 on the hep atic vascular resistance distribution and the receptor subtype respons ible for the effect in isolated rabbit livers perfused via the portal vein with 5% albumin-Krebs solution. The sinusoidal pressure was estim ated using the double vascular occlusion pressure. The basal portal ve nous resistance comprised 59% of the total portal-hepatic venous resis tance. In response to a bolus injection of ET-1 (0.05-5 mu g), which l ed to a final concentration of 0.1-10 nM in the recirculating perfusat e, the portal venous resistance increased in a dose-dependent manner, whereas the hepatic venous resistance did not change significantly at any concentration. This hepatic vasoconstriction was associated with L iver weight loss. The selective portal venous constriction induced by ET-1 was confirmed in Livers perfused retrogradely from the hepatic ve in to the portal vein. The ET-1-induced hepatic vasoconstriction was s ignificantly attenuated by the selective ETA receptor antagonist BQ-12 3 (1 mu M). The ETB receptor antagonist BQ-788 (1 mu M) also attenuate d the constriction at ET-1 concentrations less than 10 nM. The combina tion of BQ-123 and BQ-788 tended to inhibit the hepatic vasoconstricti on more effectively than BQ-123 alone. These results suggest that ET-1 selectively constricts the portal vein via both ETA and ETB receptors , with predominance of ETA receptor in isolated albumin-Krebs-perfused rabbit livers.