Adeagbo A S, Bishai I, Lees J, Olley P M, Coceani F
Can J Physiol Pharmacol. 1985 Sep;63(9):1101-5. doi: 10.1139/y85-181.
The prostaglandin (PG) endoperoxide, PGH2, and the thromboxane (TX) A2 analog, 9,11-epithio-11,12-methano-TXA2, were tested in vitro on the ductus venosus sphincter from fetal (premature and mature) and neonatal (1-day-old) lambs. PGH2 relaxed the indomethacin-contracted fetal ductus in a dose-dependent manner and its action was reduced after treatment with 15-hydroperoxyarachidonic acid. In contrast, reduced glutathione did not affect the PGH2 relaxation in the indomethacin-treated ductus, nor did it modify the response of the untreated ductus to constrictor stimuli. Unlike PGH2, the stable 9 alpha,11 alpha-epoxymethano-PGH2 analog contracted the vessel. Similarly, the TXA2 analog was a contractile agent, its action exceeding that of the PGH2 analog in potency and efficacy. The TXA2 analog was active on preparations from both premature (minimum 117 days gestation) and mature lambs, but a maximal effect was attained during the perinatal period. These results confirm the existence of a PG-mediated relaxing mechanism in the ductus venosus and suggest that the active compound is PGI2. This mechanism is likely responsible for keeping the ductus patent in the fetus. TXA2, formed within the liver parenchyma, is well suited for playing a role in postnatal closure of the vessel.
在体外对来自胎儿（早产和成熟）及新生（1日龄）羔羊的静脉导管括约肌进行了前列腺素（PG）内过氧化物PGH₂和血栓素（TX）A₂类似物9,11-环氧-11,12-甲撑-TXA₂的测试。PGH₂以剂量依赖方式使吲哚美辛收缩的胎儿导管松弛，在用15-氢过氧花生四烯酸处理后其作用减弱。相反，还原型谷胱甘肽不影响吲哚美辛处理的导管中PGH₂的松弛作用，也不改变未处理导管对收缩刺激的反应。与PGH₂不同，稳定的9α,11α-环氧甲撑-PGH₂类似物使血管收缩。同样，TXA₂类似物是一种收缩剂，其作用在效力和效果上超过PGH₂类似物。TXA₂类似物对早产（妊娠至少117天）和成熟羔羊的标本均有活性，但在围产期达到最大效应。这些结果证实了静脉导管中存在PG介导的松弛机制，并提示活性化合物是前列环素（PGI₂）。该机制可能负责维持胎儿期导管的开放。在肝实质内形成的TXA₂很适合在出生后血管闭合中发挥作用。
