Evidence of dysfunctional β2-adrenoceptor signal system in pre-eclampsia

Evidence of dysfunctional β2-adrenoceptor signal system in pre-eclampsia
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DOI:
10.1111/j.1471-0528.2000.tb11587.x
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发表时间:
2000-01-01
期刊:
BRITISH JOURNAL OF OBSTETRICS AND GYNAECOLOGY
影响因子:
--
通讯作者:
Sager, G
Sager, G
中科院分区:
其他
文献类型:
--
作者:
Aune, B;Vårtun, Å;Sager, G

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目的:确定β(2)-肾上腺素能受体结合和功能在健康妇女和子痫前期妇女之间的差异。设计:病例对照研究。单位:挪威特罗姆瑟大学医学院。参与者:两组孕妇:8例先兆子痫患者,与8名健康对照。方法:两组妇女静息过夜后抽取静脉血。子痫前期和对照组的胎龄(平均(SD))分别为36.4(3.8)和36.5(4.4)周。分娩六周后获得第二次血液样本。在分离的人单核白细胞中测定β(2)-肾上腺素受体的结合和功能。测定静脉血血浆中肾上腺素和去甲肾上腺素水平。结果:正常妊娠期间观察到功能性β(2)-肾上腺素受体密度升高[平均(SD) 390 (90) vs产后270(60)个位点/细胞],由于高亲和力状态的受体比例增加,而总受体密度不变。在子痫前期,功能性β(2)-肾上腺素受体的数量减少[平均(SD) 80 (40) vs产后240(30)个位点/细胞],原因是高亲和受体的比例不变,但总受体数量减少。在怀孕期间,与正常妊娠对照组(平均SD分别为1.2(0.3)和4.7 (1.8)pmol/10(6)细胞)相比,未刺激和异丙肾上腺素刺激的子痫前期妇女的cAMP水平均降低(分别为0.5(0.2)和1.7 (0.9)pmol/10(6)细胞)。子痫前期妇女血浆儿茶酚胺水平没有升高。结论:功能性β(2)-肾上腺素受体数量的增加可能有助于正常妊娠的血管舒张,而受体总数的减少可能是子痫前期外周血管阻力增加的几个因素之一。
Objectives: To determine how beta(2)-adrenoceptor binding and function differ between healthy women and those with pre-eclampsia.Design: Case-control study.Setting: Faculty of Medicine, University of Tromso, Norway.Participants: Two groups of pregnant women: eight cases with pre-eclampsia, matched with eight healthy controls.Methods: Venous blood was drawn from women in both groups after an overnight rest. The two groups were matched for gestational age which was (mean (SD)) 36.4 (3.8) and 36.5 (4.4) weeks for the preeclamptic and control groups, respectively. Six weeks after delivery a second blood sample was obtained. The binding and function of beta(2)-adrenoceptors were determined in isolated human mononuclear leukocytes. The levels of adrenaline and noradrenaline were determined in plasma from venous blood.Results: An elevated density of functional beta(2)-adrenoceptors was observed in normal pregnancy [mean (SD) 390 (90) vs 270 (60) sites/cell postpartum], due to an increased fraction of receptors in high affinity state, with unaltered total receptor density. The number of functional beta(2)-adrenoceptors was reduced in pre-eclampsia [mean (SD) 80 (40) vs 240 (30) sites/cell postpartum], due to a reduction in the total receptor number with an unaltered fraction of high affinity receptors. In pregnancy, both unstimulated and isoprenaline-stimulated cAMP levels were reduced in the women with pre-eclampsia (0.5 (0.2) and 1.7 (0.9) pmol/10(6) cells, respectively) compared with the normal pregnant controls (mean (SD) 1.2 (0.3) and 4.7 (1.8) pmol/10(6) cells, respectively). Plasma catecholamine levels were not elevated in the women with pre-eclampsia.Conclusions: The increased number of functional beta(2)-adrenoceptors may contribute to the vasodilatation seen in normal pregnancy, while the reduced overall number of receptors may be one of several factors that account for increased peripheral vascular resistance in pre-eclampsia.