CENTRAL ANGIOTENSIN IN FLUID BALANCE AND HYPERTENSION

中枢血管紧张素在液体平衡和高血压中的作用

• 批准号: 3339091
• 负责人: MICHAEL. IAN PHILLIPS
• 金额: $ 17.59万
• 依托单位: UNIVERSITY OF FLORIDA
• 依托单位国家: 美国
• 财政年份: 1980
• 资助国家: 美国
• 起止时间: 1980-09-01 至 1990-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3339091
• 关键词: affinity chromatography; angiotensin /renin /aldosterone hypertension; angiotensin II; antihypertensive agents; baroreceptors; blood brain barrier; brain mapping; catecholamines; corticosteroids; electrolyte balance; high performance liquid chromatography; hormone regulation /control mechanism; immunochemistry; neurotransmitters; radioimmunoassay

This proposal is to continue studies on the brain renin-angio-tensin system. In the first grant, studies were carried out to establish the existence of angiotensin II in the brain by immunocyto-chemistry, radioimmunoassay and high performance liquid chromatography. In the next grant period, it is proposed to continue these studies by investigating the functional role of brain angiotensin. It is planned to use both in vivo and in vitor experiments carried out in a complimentary fashiion in order to understand more about the basic mechanisms involved. Because there may be numerous functions of brain angiotensin, we hope to reduce the complexity of the problem by working on the hypothesis that a function of brain angiotensin is to control volume homeostasis. 1) Using the HPLC and RIA and an Ang II antibody that we have developed, we shall apply various physiological stimuli that are volume related and measure the effect on brain levels of ANG II will be carried out in primary cell culture and an attempt will be made to answer the question of whether Ang II is made intracellularly as a product of the renin-angiotensin cascade. Brain slices and a push-pull technique will be used to study release of Ang II under physiological stimuli. 3) Based on evidence that Ang II stimulates the nuclear tractus solitarius (NTS), experiments are proposed to study the actions of Ang II on the NTS and its involvement in the baroreceptor reflex. 4) The second main hypothesis of this work has been that SHR rats have a hyperactive brain Ang II. This is to be tested by applying the above experiments to the SHR and normotensive strains. In addition, longterm infusions of Ang II will be used to model the hypothesis of an overactive brain angiotensin system. 5) In collaboration with Dr. Bodor, we will manufacture new analogues of Ang II that can cross the blood brain barrier in order to find a new drug that can cause prolong inhibition of Brain Ang II.

该提议是继续研究大脑肾素 - 血管肌蛋白 系统。 在第一笔赠款中，进行了研究以建立 通过免疫细胞化学存在血管紧张素II在大脑中， 放射免疫测定和高性能液相色谱。 在下一个 授予期，建议通过研究 脑血管紧张素的功能作用。 它计划在体内使用两者 并在vitor实验中以免费的fashiion进行顺序进行 更多地了解所涉及的基本机制。 因为可能 是脑血管紧张素的许多功能，我们希望减少 通过提出以下假设： 脑血管紧张素将控制体积稳态。 1）使用HPLC和 RIA和ANG II抗体，我们将应用各种 与体积相关的生理刺激并衡量对 ANG II的大脑水平将在原代细胞培养和一个 将尝试回答是否提出ANG II的问题 细胞内作为肾素 - 血管紧张素级联反应的产物。 脑 切片和推动技术将用于研究Ang II的释放 在生理刺激下。 3）基于ANG II刺激的证据 提出了实验的核曲司托里留斯（NTS）来研究 ANG II对NTS的作用及其参与压力受体 反射。 4）这项工作的第二个主要假设是SHR大鼠 具有多动脑ANG II。 这将通过应用 上面是SHR和正常菌株的实验。 此外， ANG II的长期输注将用于建模 过度活跃的脑血管紧张素系统。 5）与博士博士合作 我们将制造可以跨越血脑的Ang II的新类似物 为了找到一种可能导致延长抑制的新药 Brain Ang II。