Lopatin D A, Ailamazian E K, Dmitrieva R I, Shpen V M, Fedorova O V, Doris P A, Bagrov A Y
DO Ott Institute of Obstetrics and Gynaecology, St. Petersburg, Russia.
J Hypertens. 1999 Aug;17(8):1179-87. doi: 10.1097/00004872-199917080-00018.
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.
Consecutive sample study. The levels of MBG 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 high-performance 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 MBG was studied in isolated rings of human umbilical arteries.
In 11 nonpregnant control individuals, plasma concentrations of MBG 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 MBG and OLC immunoreactive materials from HPLC fractions reacted with MBG 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 MBG, HPLC purified MBG immunoreactive material from preeclamptic plasma inhibited Na+/K+ ATPase purified from human mesenteric artery.
Our observations demonstrate the coexistence of two endogenous cardiotonic steroids in preeclamptic plasma, a more polar OLC and a less polar MBG-like compound. Substantial increases in plasma OLC and MBG 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.
测定正常妊娠和子痫前期内源性蟾蜍二烯羟酸内酯钠钾ATP酶抑制剂——海蟾蜍精样因子（MBG）的血浆水平，比较MBG与哇巴因样化合物（OLC）的变化，并鉴定子痫前期血浆中纯化的MBG免疫反应因子。
连续样本研究。通过固相荧光免疫分析法测定提取血浆中MBG和OLC化合物的水平。通过反相高效液相色谱法（HPLC）从子痫前期血浆中部分纯化MBG和哇巴因免疫反应物质，并研究它们与MBG和哇巴因抗体交叉反应的能力，以及抑制人肠系膜动脉钠钾ATP酶的能力。在人脐动脉分离环中研究了纯品MBG的血管收缩作用。
11名非妊娠对照个体的血浆中，MBG和OLC浓度分别为0.190±0.04 nmol/L和0.297±0.037 nmol/L。在非并发症妊娠晚期（n = 6），血浆MBG升高（0.625±0.067 nmol/L，P<0.05），而OLC未升高（0.32±0.07 nmol/L）。15名单纯性高血压患者的血浆中，MBG和OLC水平均显著升高（分别为2.63±0.10 nmol/L和0.697±0.16 nmol/L，与两个对照组相比P<0.01）。通过反相HPLC分离时，OLC在18%乙腈中洗脱，MBG在48%乙腈中洗脱。HPLC馏分中MBG和OLC免疫反应物质的系列稀释样品在固相免疫分析中以浓度依赖方式与MBG和哇巴因抗体反应。纯品MBG以浓度依赖方式引起人肠系膜动脉分离环的收缩反应。与纯品MBG类似，从子痫前期血浆中经HPLC纯化的MBG免疫反应物质抑制了从人肠系膜动脉纯化的钠钾ATP酶。
我们的观察结果表明，子痫前期血浆中存在两种内源性强心甾体，一种极性较强的OLC和一种极性较弱的MBG样化合物。子痫前期血浆中OLC和MBG免疫反应性显著增加，以及纯品MBG的血管收缩特性和人MBG免疫反应因子的钠钾ATP酶抑制活性，表明在子痫前期，MBG的血浆浓度足以显著抑制心血管组织中的钠泵，这与认为内源性洋地黄样因子在子痫前期高血压中起致病作用的观点一致。
