BRAIN POTASSIUM HOMEOSTASIS IN HYPERTENSION

高血压时脑钾稳态

• 批准号: 6109436
• 负责人: A L BETZ
• 金额: --
• 依托单位: UNIVERSITY OF MICHIGAN AT ANN ARBOR
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-07-01 至 1999-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6109436
• 关键词: adrenergic agents; antihypertensive agents; blood brain barrier; cerebral ventricles; choroid plexus; dietary supplements; disease /disorder model; homeostasis; hormone regulation /control mechanism; hydralazine; hypertension; injection /infusion; intracellular; laboratory rat; microelectrodes; neurochemistry; neuropharmacology; ouabain; potassium channel; receptor binding; sympathetic nervous system; voltage /patch clamp

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.

脑细胞外液中钾的浓度 ([K]ECF)受到严格监管，尽管 血浆钾浓度。然而，我们在三个月中观察到 脑内[K]ECF是不同的高血压动物模型 与血压正常的对照组动物相比显著降低。 此外，长期向脑组织中注入少量钾 DOCA-SALT大鼠脑室预防高血压的发生 高血压。因此，我们假设监管系统 参与控制脑内[K]ECF的分子也控制着血液 压力。 该项目旨在为这一假设提供进一步的支持 并考察了两个可能控制两者的监管系统的作用 脑[K]ECF和血压。具体目标是：1)确定 高血压患者血压与脑内[K]ECF的关系 正常血压和高血压动物以及在中枢或饮食期间 补钾。2)识别大脑中的异常 钾稳态是[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在脑内ECF调节中的作用 以前的许多临床和动物研究都提出了相反的结论 膳食钾摄入量与血压的关系我们的 研究可以确定这种关系的生理基础， 同时，提供有关如何监管[K]ECF的新信息。 [K]ECF是重要的钾相关变量的论证 最终可能导致新的治疗方法。