MODULATION OF ADRENAL ION CHANNELS IN HYPERTENSION

高血压中肾上腺离子通道的调节

基本信息

批准号：
2223398
负责人：
PETER M VASSILEV
金额：
$ 18.37万
依托单位：
BRIGHAM AND WOMEN'S HOSPITAL
依托单位国家：
美国
项目类别：
财政年份：
1991
资助国家：
美国
起止时间：
1991-08-01 至 1995-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/2223398
关键词：
G protein adrenal glands adrenocorticotropic hormone angiotensin /renin /aldosterone hypertension angiotensin II laboratory rat potassium channel second messengers secretion species difference spontaneous hypertensive rat voltage /patch clamp

项目摘要

The overall goal of this project is the characterization of membrane events initiated by aldosterone secretagogues and to determine their role in mediating the abnormalities in steroid secretion observed in experimental hypertension. The stimulating effect of angiotensin II (AII) on aldosterone secretion is blunted in adrenal zona glomerulsa (ZG) cells in spontaneously hypertensive rats compared to normotensive rats. The mechanism of this inhibition is not known. This grant will test the hypothesis that the abnormalities in SHR involve functional modifications of K(+) channels or their modulation by AII through defined second messengers. The secretagogues, AII and ACTH, influence distinct messenger systems and may exhibit different effects on membrane channels in normotensive and hypertensive rats. Therefore, channel-regulating mechanisms involving different second messengers systems under the influence of these secretagogues will be compared in normotensive and hypertensive rats. The main experimental approaches use a combination of the whole cell/patch-clamp configurations and a newly designed ultra-low volume, hanging-drop patch-clamp technique as well as affinity-purified antibodies directed against different G-protein subunits. The specific aims of the project are to investigate the effects of AII and ACTH on K(+) channels in ZG cells, to explore the involvement of distinct second messengers in the modulation of these channels and to compare the effects of secretagogues on K(+) channels in ZG cells from normotensive and hypertensive rats. The results from these studies should substantially increase our understanding of the membrane events involved in signal transduction during stimulation of aldosterone biosynthesis and of derangements in this regulation in experimental hypertension.

该项目的总体目标是膜事件的表征由醛固酮秘密促发出，并确定其在介导实验中观察到的类固醇分泌的异常高血压。血管紧张素II（AII）的刺激作用对醛固酮分泌在肾上腺Zona glomerulsa（ZG）细胞中钝化与正常的大鼠相比，自发性高血压大鼠。这这种抑制的机制尚不清楚。该赠款将测试假设SHR中的异常涉及功能修改 k（+）通道或通过AII通过定义的第二使者。秘密的AII和ACTH会影响独特的使者系统并可能对膜通道显示不同的影响正常且高血压的大鼠。因此，通道调节涉及不同第二使者系统的机制这些促分子的影响将在正常性和高血压大鼠。主要的实验方法结合了整个单元格/补丁钳配置和新设计的超低音量，悬挂式补丁钳技术以及亲和力纯化针对不同G蛋白亚基的抗体。具体该项目的目的是研究AII和ACTH对K（+）的影响 ZG细胞中的通道，探索不同的第二个在调制这些渠道的使者并比较效果 ZG细胞中K（+）通道上的秘密g（来自ZG）的g（+）通道。高血压大鼠。这些研究的结果应大大增加我们对信号涉及的膜事件的理解醛固酮生物合成和刺激期间的转导实验高血压中这种调节中的危险。