CHARACTERIZATION OF HYPOTHALAMIC NA+ TRANSPORT INHIBITOR

最近的研究表明，下丘脑可能起着中心作用。 在开发和维护某些形式的实验 高血压。来自扩容高血压动物的血浆和 据报道，患有高血压的患者体内含有一种 抑制(Na，K)ATPase的物质。血管内钠泵抑制 由这种循环因子引起的平滑肌可以产生强心剂 血管张力增加，血管对血管活性的敏感性增加 药物和动脉高血压。在某些动物模型中 高血压似乎需要一个完整的下丘脑 钠泵抑制活性的表达。牛下丘脑 含有一种酸稳定的低分子物质，它是一种有效的， 哺乳动物(Na，K)ATPase的可逆抑制物，并具有 推定的利钠激素的特性。这一因素可能是 连接肾脏、大脑和心血管系统的化学介质 实验扩容与某些形体人的起源 原发性高血压。这项建议的目的是：(1)获得 基于镁依赖可逆性的抑制因子可靠检测 纯化的(Na，K)-ATPase抑制和哇巴因敏感性抑制 人红细胞对~(86)Rb的摄取；(2)利用该分析方法促进 高效液相色谱分离纯化缓蚀剂 亲和层析和分子的化学操作；和(3) 以确定纯化的缓蚀剂的化学性质。在美国取得的成功 该项目将使直接的生理测试成为可能，以确认 抑制物在高血压疾病及其他疾病中的作用 钠代谢和膜转运现象的改变。

Recent studies have suggested that the hypothalamus may play a central role in the development and maintenance of certain forms of experimental hypertension. Plasma from volume-expanded hypertensive animals and patients with essential hypertension has been reported to contain a substance which inhibits (Na,K)ATPase. Sodium pump suppression in vascular smooth muscle caused by such a circulating factor could result in tonic increases in vascular tone, increased vascular sensitivity to vasoactive agents, and arterial hypertension. In certain of the animal models of hypertension it appears that an intact hypothalamus is required for the expression of the sodium-pump suppressing activity. Bovine hypothalamus contains a acid-stable low molecular weight substance which is a potent, reversible inhibitor of the mammalian (Na,K)ATPase, and possesses the characteristics of the putative natriuretic hormone. This factor may be a chemical mediator linking kidney, brain, and the cardiovascular system in the genesis of experimental volume-expanded and certain forms of human essential hypertension. The aims of this proposal are: (1) To obtain reliable assays of the inhibitory factor based on Mg2+ dependent reversible inhibition of purified (Na,K)ATPase, and inhibition of ouabain-sensitive 86Rb+ uptake in human erythrocytes; (2) To use the assays to facilitate purification of the inhibitor by high performance liquid chromatography, affinity chromatography, and chemical manipulation of the molecule; and (3) To determine the chemical nature of the purified inhibitor. Success in the project would make possible direct physiological testing to confirm the inhibitor's role in hypertensive disease as well as in other disorders of altered sodium metabolism and membrane transport phenomena.