ENDOGENOUS DIGOXIN-IMMUNOACTIVITY/HYPERTENSIVE PREGNANCY

几个实验室的数据表明， 女性血清中内源性地高辛样免疫反应因子（DLIF） 妊娠高血压综合征（PIH） 有证据表明肾上腺 和胎盘是DLIF的来源，这些因素是内源性的 哇巴因敏感性Na/K ATP酶抑制剂。 ATP酶是一种 小动脉中的血管平滑肌收缩。 Na/K抑制 ATP酶增强血管平滑肌收缩引起血管收缩 导致全身性高血压 考虑到这些因素， DLIF可能是血管收缩效应的原因 在妊娠高血压综合征中观察到，因此在 这种疾病的病因。 我们提出了一个工作假设：DLIF是内源性抑制剂， 哇巴因敏感的钠-钾ATP酶，通过这种机制， 妊高征时血压升高。 我们将测试第一部分 工作假设 证明DLIF是ATP酶抑制剂 需要纯化和生物学特性的这些内源性 与孕妇隔离的因素。 用于测量DLIF的总组分、蛋白结合组分和游离组分的试验 在血清和尿液中的含量。 该项目的目的是利用 这些测定用于分离、纯化和表征 从孕妇血清和尿液中获得的免疫活性因子 妇女和人类胎盘组织。 将进行表征 利用放射免疫、放射受体和钠-钾ATP酶 抑制测定。 为了提供DLIF的特异性免疫测定， 这个因素将得到发展。 因为DLIF与 血清蛋白可调节其生物活性， 将研究这些因素对血清蛋白的影响。 水平和相对 孕晚期正常人和正常妊娠妇女血清中生物活性DLIF的蛋白结合率 高血压孕妇将被确定。 这项研究将提供的物理-生化特性， DLIF和测试假设DLIF是内源性抑制剂， 钠-钾ATP酶 一般假设提出了一个联系， 内源性地高辛免疫活性，内源性ATP酶抑制剂，和 妊娠高血压综合征可以在未来的研究中解决。 这些内源性化合物可能有助于阐明 和/或提供这种疾病的标记。

Data from several laboratories have demonstrated elevated levels of endogenous digoxin-like immunoreactive factors (DLIF) in serum from women with pregnancy induced hypertension (PIH). Evidence suggests the adrenal and the placenta are sources of DLIF and that these factors are endogenous inhibitors of ouabain-sensitive Na/K ATPase. ATPase is a modulator of vascular smooth muscle contraction in arterioles. Inhibition of Na/K ATPase enhances vascular smooth muscle contraction causing vasoconstriction which leads to systemic hypertension. Given these considerations it seems plausible that DLIF might be responsible for the vasoconstriction effects observed in pregnancy induced hypertension and hence play a role in the etiology of this disease. We propose a working hypothesis: DLIF are endogenous inhibitors of ouabain-sensitive sodium-potassium ATPase and by this mechanism they increase blood pressure in PIH. We will test the first part of this working hypothesis. Demonstrating that DLIF are inhibitors of ATPase requires purification and biological characterization of these endogenous factors isolated from pregnant women. Assays for measuring the total, protein-bound, and free components of DLIF in serum and urine have been developed. The aim of this project is to use these assays to isolate, purify, and characterize the chemical nature of the immunoactive factors obtained from the serum and urine of pregnant women and from human placental tissue. Characterization will be done utilizing radioimmuno-, radioreceptor-, and sodium-potassium ATPase inhibition assays. To provide a specific immunoassay for DLIF, antibodies against this factor will be developed. Because the binding of DLIF to serum proteins may regulate its bioactivity, the binding characteristics of these factors to serum proteins will be studied. Levels and relative protein binding of bioactive DLIF in serum of third-trimester normal and hypertensive pregnant women will be determined. This research will provide the physical-biochemical characterization of DLIF and test the hypothesis that DLIF are endogenous inhibitors of sodium-potassium ATPase. The general hypothesis proposing a link between endogenous digoxin immunoactivity, endogenous ATPase inhibitors, and pregnancy induced hypertension can then be addressed in future studies. These endogenous compounds may prove useful in elucidating the mechanism of and/or provide a marker for this disease.