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表征膜事件由醛固酮促分泌剂发起并确定其在介导实验中观察到的类固醇分泌异常高血压。血管紧张素II（AII）的刺激作用肾上腺肾小球带 (ZG) 细胞的醛固酮分泌减弱自发性高血压大鼠与血压正常大鼠的比较。这这种抑制的机制尚不清楚。这笔赠款将测试 SHR 异常涉及功能改变的假设 K(+) 通道或其由 AII 通过定义的秒进行调制使者。促分泌素 AII 和 ACTH 影响不同的信使系统并可能对膜通道表现出不同的影响正常血压和高血压大鼠。因此，渠道调节涉及不同第二信使系统的机制这些促分泌剂的影响将在正常血压和高血压大鼠。主要实验方法结合使用全细胞/膜片钳配置和新设计的超低体积、悬滴膜片钳技术以及亲和纯化针对不同 G 蛋白亚基的抗体。具体的该项目的目的是研究 AII 和 ACTH 对 K(+) 的影响 ZG 细胞中的通道，探索不同的第二个通道的参与信使对这些通道的调制并比较效果正常血压和 ZG 细胞 K(+) 通道促分泌剂的作用高血压大鼠。这些研究的结果应该基本上增加我们对信号涉及的膜事件的理解刺激醛固酮生物合成过程中的转导实验性高血压中这种调节的紊乱。