McMurdo L, Thiemermann C, Vane J R
William Harvey Research Institute, St. Bartholomew's Hospital Medical College, London, UK.
Eur J Pharmacol. 1994 Jun 23;259(1):51-5. doi: 10.1016/0014-2999(94)90156-2.
The ETB receptor agonist, IRL 1620 injected into the left ventricle, induced a biphasic (transient fall followed by a secondary fall lasting 5 min) depressor response in the anaesthetised rabbit. This was followed by a rise in systemic blood pressure which returned to control levels within 30 min. In addition, IRL 1620 caused a strong, transient inhibition of ADP-induced platelet aggregation ex vivo. The selective ETA receptor antagonist, FR 139317 had no effect on either the haemodynamic or anti-aggregatory effects of IRL 1620. Indomethacin which had no effect on the initial transient depressor response induced by IRL 1620, abolished the secondary fall revealing a sustained pressor response. Indomethacin also prevented the IRL 1620-induced inhibition of platelet aggregation ex vivo. Thus, IRL 1620 is a selective ETB receptor agonist in the anaesthetised rabbit, causing vasodilatation, vasoconstriction and inhibition of ex vivo platelet aggregation. The inhibition of platelet aggregation by IRL 1620 is due to an ETB receptor-mediated release of prostacyclin into the circulation, for it is inhibited by indomethacin, but not by FR 139317.
将ETB受体激动剂IRL 1620注入麻醉兔的左心室，可诱导出双相（短暂下降后接着是持续5分钟的二次下降）降压反应。随后出现全身血压升高，30分钟内恢复到对照水平。此外，IRL 1620在体外对ADP诱导的血小板聚集有强烈的短暂抑制作用。选择性ETA受体拮抗剂FR 139317对IRL 1620的血流动力学或抗聚集作用均无影响。吲哚美辛对IRL 1620诱导的初始短暂降压反应无影响，但消除了二次下降，显示出持续的升压反应。吲哚美辛还可防止IRL 1620在体外诱导的血小板聚集抑制。因此，在麻醉兔中IRL 1620是一种选择性ETB受体激动剂，可引起血管舒张、血管收缩和体外血小板聚集抑制。IRL 1620对血小板聚集的抑制作用是由于ETB受体介导的前列环素释放到循环中，因为它被吲哚美辛抑制，但不被FR 139317抑制。
