REGULATION OF BRAIN ANGIOTENSIN II IN HYPERTENSION

高血压脑血管紧张素 II 的调节

• 批准号: 3360888
• 负责人: DENNIS P HEALY
• 金额: $ 11.62万
• 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/3360888
• 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中起重要作用 心血管系统，有大量证据 这表明神经源性机制可能有助于 高血压的发展。 活性的增加 脑血管紧张素 II (Ang II) 系统被认为是 发展和维持的可能致病因素 自发性高血压大鼠（SHR）的高血压。 这 目前的实验旨在利用高分辨率 监测大脑活动的定量成像技术 高血压大鼠的 Ang II 系统以确定是否 该系统监管的改变可以与 高血压的发展或维持。 我们建议：1) 通过定位识别中枢神经系统中假定的血管紧张素能神经元 通过原位杂交获得血管紧张素原A-ogen) mRNA；共同 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观察血管紧张素II受体的分布。 2） 定量 Ang II 的神经元水平 放射免疫组化并监测 Ang II 和 Ang 水平 I 中枢血管紧张素转换酶抑制后 为了估计 Ang II 的神经元周转。 3）有 制定了这些定量程序，重点关注具体的 中央自主控制区域的血管紧张素系统，我们 然后将通过以下方式监测大脑 Ang II 系统的活动 Ang II 和/或 A-ogen 神经元水平的相关变化 以下高血压中 Ang II 受体变化的 mRNA 模型：从胎儿到不同阶段的SHR和Wistar京都大鼠 成人; DOCA-盐大鼠；和 Dahl 盐敏感且耐盐 高盐饮食和低盐饮食的大鼠。 我们将要研究的大脑区域 重点关注含有血管紧张素能神经元件， 生理上与心血管控制有关；包括 室旁器官、视上器官、室周器官、 穹窿周围区和孤立迷走神经区。 同时进行的 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 为大脑Ang的调节提供重要的新见解 高血压II系统。