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Role of the angiotensin II of the central nervous system

血管紧张素II对中枢神经系统的作用

基本信息

批准号：
08458258
负责人：
TERUI Naohito
金额：
$ 4.74万
依托单位：
Inst.of Basic Med.Sci., Univ.of Tsukuba
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B)
财政年份：
1996
资助国家：
日本
起止时间：
1996 至 1998
项目状态：
已结题

项目摘要

The function of the peripherally circulating renin- angiotensin is the regulation of body-fluid homeostasis. They control hemodynamics by influencing many aspects such as the control of vascular tone, stimulation of sodium reabsorption by the kidney, and of aldosterone production from the adrenal cortex. In addition to such cardio-vascular regulation, . it has now been shown that angiotensin II is functioning as a neurotransmitter-like substance in in the brain. Angiotensin II (AgII)-like immunoreactivity is observed in the central nervous system. The receptor ligand binding experiment also revealed AgII binding sites in the brain, and messages of Ag II receptors were detected in the nervous system. Ag II receptors are now classified into four groups ; Angiotnsin receptor 1(la and 1b), 2, 3 and 4. In the present project, we tried to clarify the location of the Ag II receptor la (AT1a) in the central nervous system and function of AT1a in the baroreceptor reflex, using AT1a gene knock out mice (Sugaya et al. J.B.C.vol 270 : 18719-18722, 1995).1) We succeeded to record the haeart rate and the blood pressure directly from the femoral artery in ananesthesized and free moving mice, then analyze the barorecptor function.2) The gain of the baroreceptor reflex in knockout mice is smaller than that of wilde mice.3) Locarization of the ATl a in the central nervous system is much wider in comparing with results obtained by mmunohistochemical methods or in situ hybridization by messenger RNA probe.

外周循环的肾素-血管紧张素的功能是调节体液稳态。它们通过影响许多方面来控制血液动力学，例如控制血管张力、刺激肾脏对钠的重吸收和肾上腺皮质产生醛固酮。除了这种心血管调节之外，现在已经显示血管紧张素II在脑中作为神经递质样物质起作用。在中枢神经系统中观察到血管紧张素II（AgII）样免疫反应性。受体配体结合实验还揭示了大脑中的Ag II结合位点，并在神经系统中检测到Ag II受体的信息。Ag II受体现在分为四组：血管紧张素受体1（Ia和Ib）、2、3和4。本课题以Ag Ⅱ受体1a（Ag Ⅱ receptor 1a，AT 1a）基因敲除小鼠为研究对象，试图阐明AT 1a在中枢神经系统中的定位及其在压力感受性反射中的作用（Sugaya等人，J. B.C.第270卷：18719-18722，1995）。1）我们成功地直接从麻醉和自由活动的小鼠的股动脉记录心率和血压，2）敲除小鼠压力感受器反射增益小于野生型小鼠; 3）AT 1a在中枢神经系统的定位范围比免疫组化法和信使RNA探针原位杂交法更广。