PHYSIOLOGIC ROLE OF ENDOGENOUS DIGITALIS-LIKE FACTOR

人类肾上腺合成和分泌多种重要的 调节荷尔蒙。我们已经证明，肾上腺皮质是一种组织 富含内源性地高辛样免疫反应因子(DLIF)，即 分泌DLIF进入血液循环。我们还将DLIF提纯为 均一性，测定了其相对分子质量和化学组成。这个 内源性DLIF的化学成分与 具有心脏活性的卡登内酯。几项研究表明， 高血压病患者血清内源性DLIF水平的研究 高血压(EH)、妊娠高血压综合征(PIH)和 心血管功能障碍。DLIF可能调节细胞的酶活性 哇巴因敏感的钠钾ATPase。Na/K-ATPase(钠泵)是一种 小动脉血管平滑肌张力的重要调节剂以及 其他心血管事件。钠泵抑制导致 血管收缩导致全身性高血压。因此，DLIF 可能在EH和PIH的发病机制中起一定作用。 我们提出了一个工作假设：来自人肾上腺皮质的DLIF是 哇巴因敏感型钠钾ATPase的内源性抑制物 这种机制会影响哺乳动物的血压。 这个项目的目的是定义详细的分子结构 DLIF并鉴定该因子的生物活性 肾上腺组织。将使用四个独立的 洋地黄样活性的测定；免疫反应性，受体结合， 钠钾ATPase酶活性和钠泵活性。 这项研究将提供急需的生化鉴定 来自肾上腺皮质的DLIF，将这些因素与来自血浆的DLIF进行比较 检验肾上腺来源的DLIF是内源性抑制因子的假设 钠钾ATPase。这些因素可能被证明有助于阐明 负责EH或PIH的机制，并提供急需的诊断 这些疾病的标志物。

The human adrenal synthesizes and secretes a variety of important regulatory hormones. We have shown that the adrenal cortex is a tissue rich in endogenous digoxin-like immunoreactive factor (DLIF) and that is secretes DLIF into the circulation. We have also purified DLIF to homogeneity, determined its molecular weight and chemical composition. The chemical composition of endogenous DLIF is remarkably similar to that of the cardioactive cardenolides. Several studies have demonstrated elevated levels of endogenous DLIF in serum from patients with essential hypertension (EH), pregnancy induced hypertension (PIH), and during cardiovascular dysfunction. DLIF may regulate the enzymatic activity of ouabain-sensitive sodium-potassium ATPase. Na/K-ATPase (sodium pump) is an important modulator of vascular smooth muscle tone in arterioles as well as other cardiovascular events. Inhibition of the sodium pump causes vasoconstriction which leads to systemic hypertension. Therefore, DLIF from the adrenal cortex may play a role in the etiology of EH and PIH. We propose a working hypothesis: DLIF from human adrenal cortex are endogenous inhibitors of ouabain-sensitive sodium-potassium ATPase and by this mechanism they affect blood pressure in mammals. The aim of this project is to define the detailed molecular structure of DLIF and characterize the biological activity of this factor obtained from adrenal tissues. Characterization will be done using four independent assays of digitalis-like activity; immunoreactivity, receptor binding, sodium-potassium ATPase enzymatic activity, and sodium pump activity. This research will provide the much needed biochemical identification of DLIF from adrenal cortex, compare these factors to DLIF from plasma, and test the hypothesis that DLIF from adrenals are endogenous inhibitors of sodium-potassium ATPase. These factors may prove useful in elucidating the mechanism responsible for EH or PIH and provide much needed diagnostic markers for these diseases.