Coceani F, Kelsey L, Seidlitz E
Research Institute, Hospital for Sick Children, Toronto, Ont., Canada.
Can J Physiol Pharmacol. 1992 Jul;70(7):1061-4. doi: 10.1139/y92-146.
The ductus arteriosus is a special muscular shunt that in the fetus allows blood to bypass the unexpanded lungs. It closes rapidly after birth and this event is initiated by the physiologic rise in blood oxygen tension. Endothelin-1 has been proposed by us as a local mediator for oxygen after demonstrating that it is formed within the ductus and is a potent ductus constrictor. To confirm this possibility, we have now measured the release of endothelin-1 from the isolated ductus of near-term fetal lambs at different oxygen concentrations of the medium. In addition, using the same preparation, we have examined the effect on contractile tone of compounds interfering with the synthesis (phosphoramidon, 50 microM) and action (BQ123, 1 microM) of endothelin-1. We report that release of endothelin-1 from the ductus tends to increase with the oxygen concentration up to a value mimicking the neonatal condition. Phosphoramidon and, to a greater degree, BQ123 inhibit the contraction of the vessel to oxygen. These results implicate endothelin-1 as the effector agent for oxygen in the ductus and, by extension, assign to this peptide a critical role in the closure of the vessel at birth.
动脉导管是一种特殊的肌肉分流通道，在胎儿期可使血液绕过未扩张的肺脏。出生后它迅速关闭，这一过程由血氧张力的生理性升高启动。我们在证实内皮素 -1 在动脉导管内形成且是一种强效的动脉导管收缩剂后，提出它作为氧的局部介质。为证实这种可能性，我们现在测量了不同氧浓度培养基中近足月胎羊离体动脉导管内皮素 -1 的释放量。此外，使用相同的标本，我们研究了干扰内皮素 -1 合成（磷酰胺脒，50 μM）和作用（BQ123，1 μM）的化合物对收缩张力的影响。我们报告，动脉导管内皮素 -1 的释放量随氧浓度升高而增加，直至达到模拟新生儿状态的值。磷酰胺脒以及程度更大的 BQ123 抑制血管对氧的收缩。这些结果表明内皮素 -1 是动脉导管中氧的效应剂，进而赋予该肽在出生时动脉导管关闭过程中的关键作用。
