REGULATION OF BRAIN ANGIOTENSIN II IN HYPERTENSION

高血压脑血管紧张素 II 的调节

• 批准号: 3360883
• 负责人: DENNIS P HEALY
• 金额: $ 12.21万
• 依托单位: MOUNT SINAI SCHOOL OF MEDICINE OF CUNY
• 依托单位国家: 美国
• 财政年份: 1989
• 资助国家: 美国
• 起止时间: 1989-04-01 至 1992-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3360883
• 关键词: angiotensin /renin /aldosterone hypertension; angiotensin II; autoradiography; central nervous system; histochemistry /cytochemistry; hormone regulation /control mechanism; neural transmission; neurochemistry; neurogenic hypertension; neurons; nucleic acid hybridization; spontaneous hypertensive rat

The central nervous system plays a major role in the regulation of the cardiovascular system and there is a great deal of evidence that indicate that neurogenic mechanisms may contribute to the development of hypertension. An increase in the activity of the brain angiotensin II (Ang II) system has been implicated as a possible causative factor in the development and maintenance of hypertension in the spontaneously hypertensive rat (SHR). The present experiments are designed to utilize high resolution quantitative imaging technique to monitor the activity of the brain Ang II system in hypertensive rats in order to determine whether an alteration in the regulation of this system can be linked to the development or maintenance of hypertension. We propose to: 1) Identify putative angiotensinergic neurons in CNS by localizing angiotensinogen A-ogen) mRNA by in situ hybridization; co- localizing A-ogen mRNA with either immunoreactive A-ogen or Ang II; and correlating the distribution of these neurons with the distribution of Ang II receptors by receptor autoradiography. 2) Quantitate the neuronal levels of Ang II by radioimmunohistochemistry and monitor the level of Ang II and Ang I following central angiotensin-converting enzyme inhibition in order to estimate the neuronal turnover of Ang II. 3) Having established these quantitative procedures to focus on specific angiotensinergic systems in areas of central autonomic control, we will then monitor the activity of the brain Ang II system by correlating changes in the neuronal levels of Ang II and/or A-ogen mRNA with changes in Ang II receptors in the following hypertensive models: SHR and Wistar Kyoto rats at various stages from fetal to adult; DOCA-salt rats; and Dahl salt-sensitive and salt-resistant rats on high and low salt diets. The brain areas that we will focus on contain angiotensinergic nerve elements and are physiologically linked to cardiovascular control; including the paraventricular n., supraoptic n., circumventricular organs, perifornical area, and solitary-vagal area. The simultaneous examination of these variables of neurotransmission (i.e. peptide synthesis, storage, turnover and postsynaptic receptors) should provide important new insights into the regulation of the brain Ang II system in hypertension.

中枢神经系统在调节 有大量证据表明 这表明神经机制可能有助于 发生高血压。 增加的活动， 脑血管紧张素II（Ang II）系统被认为是一种 可能的致病因素的发展和维持 自发性高血压大鼠（SHR）。 的 目前的实验旨在利用高分辨率 定量成像技术来监测大脑的活动 血管紧张素Ⅱ系统在高血压大鼠，以确定是否 这一制度的调整可以与 发展或维持高血压。 我们建议：1） 通过定位鉴定CNS中假定的血管紧张素能神经元 血管紧张素原A-ogen）mRNA;共 用免疫反应性A-ogen或Ang Ⅱ定位A-ogen mRNA; 并将这些神经元的分布与 通过受体放射自显影术测定血管紧张素II受体的分布。 （二） 通过以下方法定量Ang II的神经元水平： 放射免疫组化法检测血管紧张素Ⅱ和血管紧张素Ⅱ水平 I在中枢血管紧张素转换酶抑制后， 以估计Ang II的神经元周转。 3)具有 建立了这些定量程序， 血管紧张素能系统在中央自主控制领域，我们 然后将监测大脑血管紧张素II系统的活动， 与Ang II和/或A-原的神经元水平的变化相关 原发性高血压患者血管紧张素Ⅱ受体mRNA表达的变化 模型：SHR和Wistar京都大鼠在不同阶段，从胎儿到 成年; DOCA盐大鼠;和Dahl盐敏感和盐抗性 高盐和低盐饮食的大鼠。 我们将在大脑中 集中于含有血管紧张素能神经成分， 生理上与心血管控制有关;包括 室旁神经，视上神经，室周器官， 穹窿周围区和孤迷走神经区。 同时 检查这些神经传递变量（即肽 合成、储存、周转和突触后受体）应 为脑血管紧张素的调节提供了重要的新见解， II系统在高血压中的作用。