REGULATION OF BRAIN ANGIOTENSIN II IN HYPERTENSION

中枢神经系统在调节脑血管紧张素转换酶活性方面起着重要作用 心血管系统，有大量证据表明 这表明神经源性机制可能有助于 高血压的发展。一个活动的增加， 脑血管紧张素II(Ang II)系统被认为是一种 开发和维护的可能原因 自发性高血压大鼠(SHR)的高血压。这个 目前的实验旨在利用高分辨率 用于监测大脑活动的定量成像技术 血管紧张素Ⅱ系统在高血压大鼠体内的表达 对这一制度的监管的变化可以与 高血压的发展或维持。我们建议：1) 定位鉴定中枢神经系统内可能的血管紧张素能神经元 血管紧张素原A-原)m RNA原位杂交； 用免疫反应性A原或Ang II定位A原mRNA； 并将这些神经元的分布与 受体放射自显影测定血管紧张素Ⅱ受体的分布2) 血管紧张素转换酶II的神经元水平 放射免疫组织化学检测血管紧张素Ⅱ和血管紧张素转换酶水平 中枢性血管紧张素转换酶抑制后 为了估计血管紧张素转换酶的神经元周转率。 建立了这些量化程序，以侧重于具体的 中枢自主神经控制区的血管紧张素能系统 然后通过以下方式监测大脑Ang II系统的活动 血管紧张素Ⅱ和/或血管紧张素原神经元水平的相关性变化 高血压患者血管紧张素Ⅱ受体基因表达的变化 模型：自发性高血压大鼠和Wistar京都大鼠 成年；DOCA-盐大鼠；Dahl盐敏感和耐盐 高盐饮食和低盐饮食的大鼠。我们将会看到的大脑区域 重点是含有血管紧张素能神经成分和 在生理上与心血管控制有关；包括 室旁，视上，室周器官， 穹隆周区和孤立性迷走区。《同时》 神经传递(即多肽)的这些变量的检测 合成、储存、周转和突触后受体)应该 为大脑和大脑的调节提供重要的新见解 高血压的II系统。

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.