Circulating bufodienolide and cardenolide sodium pump inhibitors in preeclampsia
Circulating bufodienolide and cardenolide sodium pump inhibitors in preeclampsia
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DOI：
10.1097/00004872-199917080-00018
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发表时间：
1999-08-01
影响因子：
4.9
通讯作者：
Bagrov, AY
中科院分区：
文献类型：
--
作者：
Lopatin, DA;Ailamazian, EK;Bagrov, AY
目的测定正常血压妊娠和先兆子痫患者血浆中内源性蟾蜍二烯内酯Na+/K+ ATP酶抑制剂海蟾蜍素样因子（MBG）的水平，比较MBG与哇巴因样化合物（OLC）的变化，并对从先兆子痫血浆中纯化的MBG免疫反应因子进行表征。 连续抽样研究。通过固相荧光免疫测定法测量提取的血浆中 MEG 和 OLC 化合物的水平。通过反相高效液相色谱 (HPLC) 从先兆子痫血浆中部分纯化 MBG 和哇巴因免疫反应材料，并研究它们与 MBG 和哇巴因抗体交叉反应以及抑制人肠系膜动脉 Na+/K+ ATP 酶的能力。在离体的人脐动脉环中研究了纯 MEG 的血管收缩作用。结果 在 11 名非妊娠对照个体中，MEG 和 OLC 的血浆浓度分别为 0.190 +/- 0.04 nmol/l 和 0.297 +/- 0.037 nmol/l。在无并发症妊娠的晚期 (n = 6)，血浆 MBG 增加 (0.625 +/- 0.067 nmol/l，P < 0.05)，而 OLC 没有增加 (0.32 +/- 0.07 nmol/l)。 在 15 名先兆子痫患者中，MBG 和 OLC 的血浆水平均显着增加 (2.63 +/- 0.10 nmol/l 和 分别为 0.697 +/- 0.16 nmol/l，与两个对照组相比，P < 0.01）。当通过反相HPLC分级时，OLC用18％乙腈洗脱，MBG用48％乙腈洗脱。来自HPLC级分的MEG和OLC免疫反应材料的系列稀释样品在固相免疫测定中以浓度依赖性方式与MEG和哇巴因抗体反应。真实的 MBG 以浓度依赖性方式引起人肠系膜动脉孤立环的收缩反应。与真实的 MEG 类似，HPLC 从先兆子痫血浆中纯化了 MBG 免疫反应物质，抑制了从人肠系膜动脉纯化的 Na+/K+ ATP 酶。 结论 我们的观察结果表明，先兆子痫血浆中存在两种内源性强心类固醇，即极性较大的 OLC 和极性较小的类 MEG 化合物。先兆子痫中血浆 OLC 和 MEG 免疫反应性的显着增加，以及真实 MBG 的血管收缩特性和人 MBG 免疫反应因子的 Na+,K+ ATP 酶抑制活性，表明在先兆子痫中，MBG 的血浆浓度足以显着抑制心血管组织中的钠泵，并且与 认为内源性洋地黄样因子在先兆子痫高血压中具有致病作用。 I Hypertens 1999, 17:1179-1187 (C) Lippincott Williams & Wilkins。
Objective To determine plasma levels of the endogenous bufodienolide Na+/K+ ATPase inhibitor, marinobufagenin-like factor (MBG), in normotensive pregnancy and in preeclampsia, to compare changes of MBG with that of ouabain-like compound (OLC), and to characterize the purified MBG immunoreactive factor from preeclamptic plasma.Design and methods Consecutive sample study. The levels of MEG and OLC compounds were measured in extracted plasma by solid phase fluoroimmunoassays. MBG and ouabain immunoreactive materials were partially purified from preeclamptic plasma via reverse-phase highperformance liquid chromatography (HPLC) and studied for their ability to cross react with MBG and ouabain antibodies, and to inhibit the Na+/K+ ATPase from human mesenteric arteries. Vasoconstrictor effect of authentic MEG was studied in isolated rings of human umbilical arteries.Results In 11 nonpregnant control individuals, plasma concentrations of MEG and OLC were 0.190 +/- 0.04 nmol/l and 0.297 +/- 0.037 nmol/l, respectively. In the third trimester of noncomplicated pregnancy (n = 6), plasma MBG increased (0.625 +/- 0.067 nmol/l, P < 0.05), and OLC did not (0.32 +/- 0.07 nmol/l), In 15 patients with preeclampsia, plasma levels of both MBG and OLC increased dramatically (2.63 +/- 0.10 nmol/l and 0.697 +/- 0.16 nmol/l, respectively, P < 0.01 versus both control groups). When fractionated by reverse phase HPLC, OLC was eluted by 18% acetonitrile, and MBG by 48% acetonitrile, Serially diluted samples of MEG and OLC immunoreactive materials from HPLC fractions reacted with MEG and ouabain antibody in solid phase immunoassay in a concentration dependent fashion. Authentic MBG caused contractile responses of isolated rings of human mesenteric arteries in a concentration-dependent manner. Similarly to the authentic MEG, HPLC purified MBG immunoreactive material from preeclamptic plasma inhibited Na+/K+ ATPase purified from human mesenteric artery.Conclusions Our observations demonstrate the coexistence of two endogenous cardiotonic steroids in preeclamptic plasma, a more polar OLC and a less polar MEG-like compound. Substantial increases in plasma OLC and MEG immunoreactivity in preeclampsia, along with the vasoconstrictor properties of authentic MBG and Na+,K+ ATPase inhibitory activity of human MBG immunoreactive factor, suggest, that in preeclampsia, plasma concentrations of MBG are enough to substantially inhibit the sodium pump in cardiovascular tissues, and are in accordance with the views attributing endogenous digitalis-like factors a pathogenic role in the preeclamptic hypertension. I Hypertens 1999, 17:1179-1187 (C) Lippincott Williams & Wilkins.