BRAIN POTASSIUM HOMEOSTASIS IN HYPERTENSION

大脑细胞外液中钾的浓度 （[K]ECF）受到严格调控，尽管急性或慢性变化， 血浆钾浓度 然而，我们观察到， 不同高血压动物模型的脑[K]ECF 与血压正常的对照动物相比显著降低。 此外，慢性输注少量钾到 DOCA-盐大鼠的脑室阻止了 高血压因此，我们假设监管系统 参与控制脑中的[K]ECF也控制血液 压力 本项目旨在为这一假设提供进一步的支持 并研究可能控制两者的两个监管系统的作用 脑[K]ECF和血压。 具体目标是：1）确定 脑[K]ECF与血压关系 血压正常和高血压动物，以及在中枢或饮食期间 补钾 2)发现大脑异常 钾稳态，这是[K]ECF降低的原因， 高血压动物 3)确定交感神经的作用 系统和脑哇巴因样因子对脑[K]ECF调节 许多以前的临床和动物研究表明， 膳食钾摄入量与血压的关系。 我们 研究可以确定这种关系的生理基础， 与此同时，提供了关于[K]ECF如何监管的新信息。 [K]ECF是钾的重要相关变量的论证 最终可能会带来新的治疗方法。

The concentration of potassium in the brain's extracellular fluid ([K]ECF) is tightly regulated despite acute or chronic changes in the plasma potassium concentration. However, we have observed in three different animal models of hypertension that [K]ECF in brain is significantly reduced compared to normotensive control animals. Furthermore, chronic infusions of small amounts of potassium into the cerebral ventricles of DOCA-salt rats prevents the development of hypertension. Consequently, we hypothesize that the regulatory systems that are involved in controlling [K]ECF in brain also control blood pressure. This project is designed to provide further support for this hypothesis and to examine the roles of two regulatory systems that may control both brain [K]ECF and blood pressure. The specific aims are to: 1) determine the relationship between blood pressure and [K]ECF of brain in normotensive and hypertensive animals and during central or dietary potassium supplementation. 2) identify the abnormality in brain potassium homeostasis which accounts for the decreased [K]ECF in hypertensive animals. 3) determine the roles of the sympathetic nervous system and brain ouabain-like factor in regulation of brain [K]ECF. Many previous clinical and animal studies have suggested an inverse relation between dietary potassium intake and blood pressure. Our studies could define the physiological basis for this relationship while, at the same time, providing new information on how [K]ECF is regulated. The demonstration that [K]ECF is the important potassium-related variable in hypertension could ultimately lead to new therapeutic approaches.