Endothelin-1 selectively contracts portal vein through both ETA and ETB receptors in isolated rabbit liver.
We determined the constrictive effects of endothelin (ET)-1 on the hepatic vascular resistance distribution and the receptor subtype responsible for the effect in isolated rabbit livers perfused via the portal vein with 5% albumin-Krebs solution. The sinusoidal pressure was estimated using the double vascular occlusion pressure. The basal portal venous resistance comprised 59% of the total portal-hepatic venous resistance. In response to a bolus injection of ET-1 (0.05-5 micrograms), which led to a final concentration of 0.1-10 nM in the recirculating perfusate, 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 liver weight loss. The selective portal venous constriction induced by ET-1 was confirmed in livers perfused retrogradely from the hepatic vein to the portal vein. The ET-1-induced hepatic vasoconstriction was significantly attenuated by the selective ETA receptor antagonist BQ-123 (1 microM). The ETB receptor antagonist BQ-788 (1 microM) also attenuated the constriction at ET-1 concentrations less than 10 nM. The combination of BQ-123 and BQ-788 tended to inhibit the hepatic vasoconstriction 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.
Wang
H G
HG
Department of Physiology, Shinshu University School of Medicine, Matsumoto, Japan.
Shibamoto
T
T
Miyahara
T
T
D000818:Animals; D001646:Bile / Q000378:metabolism; D001794:Blood Pressure / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D065128:Endothelin Receptor Antagonists; D019332:Endothelin-1 / Q000494:pharmacology*; D066298:In Vitro Techniques; D008099:Liver / Q000098:blood supply / Q000187:drug effects / Q000502:physiology*; D009119:Muscle Contraction / Q000187:drug effects*; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000502:physiology; D009929:Organ Size / Q000187:drug effects; D010456:Peptides, Cyclic / Q000494:pharmacology; D011169:Portal Vein / Q000187:drug effects / Q000502:physiology*; D011817:Rabbits; D044022:Receptor, Endothelin A; D044023:Receptor, Endothelin B; D017466:Receptors, Endothelin / Q000187:drug effects / Q000502:physiology*; D012039:Regional Blood Flow / Q000187:drug effects; D014655:Vascular Resistance / Q000187:drug effects; D014661:Vasoconstriction / Q000187:drug effects
D065128:Endothelin Receptor Antagonists; D019332:Endothelin-1; D010456:Peptides, Cyclic; D044022:Receptor, Endothelin A; D044023:Receptor, Endothelin B; D017466:Receptors, Endothelin; C072247:cyclo(Trp-Asp-Pro-Val-Leu)