Gupta Saurabh, Hanff Lidwien M, Visser Willy, Steegers Eric A P, Saxena Pramod R, Vulto Arnold G, MaassenVanDenBrink Antoinette
Department of Pharmacology, Erasmus MC University Medical Center, The Netherlands.
J Hypertens. 2006 Jul;24(7):1345-53. doi: 10.1097/01.hjh.0000234115.40648.88.
To investigate the functional reactivity of 5-hydroxytryptamine (serotonin; 5-HT) receptors in foetal umbilical cord arteries (UCA) and maternal subcutaneous fat resistance arteries (SFA) in normotensive and pre-eclamptic pregnancy.
Study groups were divided based on the presence or absence of pre-eclampsia and the duration of gestation.
Segments of UCA and SFA were mounted in tissue baths and concentration-response curves to 5-HT and sumatriptan (5-HT1B/1D receptor agonist) were constructed in the absence or presence of ketanserin (5-HT2A receptor antagonist) or GR125743 (5-HT1B/1D receptor antagonist).
Both 5-HT and sumatriptan contracted all UCA segments studied. The responses to 5-HT and the potency of ketanserin in UCA were not different between the study groups, indicating a similar profile of the 5-HT2A receptor. In contrast, the potencies of sumatriptan and GR125743 were significantly higher in normotensive full-term pregnancies than in normotensive pre-term pregnancies in UCA. The response to sumatriptan in UCA arteries was not significantly different between pre-eclamptic and normotensive pregnancies. However, the potency of both sumatriptan and GR125743 was positively correlated to the gestational age in the normotensive group, whereas this relationship was absent in the pre-eclamptic group. In SFA, responses to 5-HT and sumatriptan were not different between the pre-eclamptic patients and normotensive controls.
In both UCA and SFA, 5-HT1B/1D and 5-HT2A receptors mediate vasoconstriction. The sensitivity of 5-HT1B/1D receptors increases in the last trimester in the UCA in normal pregnancies, which seems to be expedited in pre-eclamptic patients. Further studies on 5-HT1B/ID receptors will thus give new insights into the foetal development and pathophysiology of pre-eclampsia.
研究正常妊娠和子痫前期妊娠中胎儿脐动脉(UCA)和母体皮下脂肪阻力动脉(SFA)中5-羟色胺(血清素;5-HT)受体的功能反应性。
根据子痫前期的有无和妊娠持续时间对研究组进行划分。
将UCA和SFA的节段安装在组织浴中,在不存在或存在酮色林(5-HT2A受体拮抗剂)或GR125743(5-HT1B/1D受体拮抗剂)的情况下构建对5-HT和舒马曲坦(5-HT1B/1D受体激动剂)的浓度-反应曲线。
5-HT和舒马曲坦均使所有研究的UCA节段收缩。研究组之间UCA对5-HT的反应和酮色林的效力无差异,表明5-HT2A受体的情况相似。相比之下,在UCA中,正常足月妊娠时舒马曲坦和GR125743的效力显著高于正常早产妊娠。子痫前期妊娠和正常妊娠的UCA动脉对舒马曲坦的反应无显著差异。然而,在正常血压组中,舒马曲坦和GR125743的效力均与胎龄呈正相关,而子痫前期组中不存在这种关系。在SFA中,子痫前期患者和正常血压对照组对5-HT和舒马曲坦的反应无差异。
在UCA和SFA中,5-HT1B/1D和5-HT2A受体均介导血管收缩。正常妊娠时UCA中5-HT1B/1D受体的敏感性在妊娠晚期增加,子痫前期患者似乎加速了这种增加。因此,对5-HT1B/ID受体的进一步研究将为胎儿发育和子痫前期的病理生理学提供新的见解。