Smith G C, McGrath J C
Autonomic Physiology Unit, University of Glasgow, Scotland.
J Cardiovasc Pharmacol. 1991 Jun;17(6):861-6. doi: 10.1097/00005344-199106000-00001.
We wished to determine the effect of prostaglandin E2 (PGE2) on the response of the ductus arteriosus to norepinephrine (NE) and whether any effect of PGE2 was influenced by O2 tension. The vessel was isolated from fetal New Zealand White rabbits and studied in vitro. The response to NE was assessed in terms of both sensitivity (pEC50) and maximum contractile response (MCR) as determined from cumulative concentration-response curves. PGE2 caused a concentration-dependent inhibition of ductal sensitivity to NE. This was maximal in nanomolar concentrations of PGE2, in which ductal sensitivity to NE was decreased by approximately 50 times. This action was only minimally potentiated by 3% O2 (simulating fetal O2 tension, PO2). PGE2 could also inhibit the MCR to NE, but this was entirely dependent on PO2. In 95% O2, PGE2 had no effect on the MCR to NE, whereas in fetal PO2, PGE2 decreased the MCR. This decrease was maximal in 1 nM PGE2, in which the MCR in 3% O2 was about one fifth the size of the MCR in 95% O2. In 1 nM nM PGE2, 10% O2 also largely abolished the inhibitory effect of PGE2 on ductal MCR to NE, indicating that this effect of O2 is also observed in the range of the physiologic increase of arterial PO2, tension that occurs at birth. PGE2 also inhibited ductal sensitivity to 5-hydroxytryptamine, histamine, and potassium. We conclude that physiologic and therapeutic concentrations of PGE2 inhibit sensitivity of the ductus arteriosus to certain vasoconstrictors and can inhibit the maximum response to NE in fetal but not increased PO2.
我们希望确定前列腺素E2（PGE2）对动脉导管对去甲肾上腺素（NE）反应的影响，以及PGE2的任何作用是否受氧张力影响。该血管取自新西兰白兔胎儿并进行体外研究。根据累积浓度-反应曲线确定的敏感性（pEC50）和最大收缩反应（MCR）来评估对NE的反应。PGE2对导管对NE的敏感性产生浓度依赖性抑制。在纳摩尔浓度的PGE2中这种抑制作用最大，此时导管对NE的敏感性降低约50倍。3%的氧气（模拟胎儿氧张力，PO2）仅轻微增强了这种作用。PGE2也能抑制对NE的MCR，但这完全取决于PO2。在95%氧气环境中，PGE2对NE的MCR无影响，而在胎儿PO2环境中，PGE2降低了MCR。这种降低在1 nM PGE2时最大，此时3%氧气环境中的MCR约为95%氧气环境中MCR的五分之一。在1 nM PGE2中，10%的氧气也在很大程度上消除了PGE2对导管对NE的MCR的抑制作用，表明在出生时发生的动脉PO2生理性升高范围内也观察到了氧气的这种作用。PGE2还抑制导管对5-羟色胺、组胺和钾的敏感性。我们得出结论，生理和治疗浓度的PGE2会抑制动脉导管对某些血管收缩剂的敏感性，并能抑制胎儿期而非PO2升高时对NE的最大反应。
