ROLE OF TISSUE ANGIOTENSINS IN THE MEDULLA OBLONGATA

组织血管紧张素在延髓中的作用

• 批准号: 6272954
• 负责人: DAVID B AVERILL
• 金额: $ 13.74万
• 依托单位: WAKE FOREST UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-04-01 至 1999-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6272954
• 关键词: angiotensin /renin /aldosterone hypertension; angiotensins; baroreflex; familial hypertension; genetically modified animals; hormone receptor; laboratory rat; medulla oblongata; molecular genetics; neuroanatomy; neurons; neuroregulation; peptide hormone; solitary tract nucleus; sympathetic nervous system

This project will test two hypotheses. First, outflow of vasomotor neurons of the rostral ventrolateral medulla (RVLM) of Ren-2 transgenic (TG) rats is augmented by angiotensin- and vasopressin-containing pathways. Second, angiotensin and vasopressin inputs to cardiovascular neurons of the nucleus tractus solitarii (nTS) and the RVLM attenuate baroreceptor reflex control of blood pressure and augment sympathetic nerve activity in TG rats. To test these hypotheses, we propose the following specific aims. 1. Describe the brainstem and hypothalamic nuclei that provide either angiotensin- or vasopressin-containing projections to presympathetic neurons of the RVLM. Retrograde tract tracing and immunocytochemical techniques will be used to define these neuroanatomical pathways. Results of these experiments will provide a neuroanatomical basis for interpreting the physiologic and neuropharmacologic experiments of the following specific aims. 2. Demonstrated that angiotensin-containing pathways to the nTS and RVLM attenuate baroreflex control of heart rate and sympathetic nerve activity in TG rats. The receptor subtypes responsible for this action of Ang II or other Ang peptides will be characterized by using receptor subtype selective antagonists. We will also demonstrate that angiotensin- containing pathways to the RVLM result in enhanced sympathetic outflow in TG rats. 3. Demonstrate that vasopressin-containing pathways to the nTS and RVLM contribute to enhanced sympathetic outflow in TG rats. Specifically, we will attempt to show that vasopressin-containing pathways to the nTS attenuate normal baroreflex function whereas vasopressin-containing pathways to the RVLM provide excitatory drive to presympathetic neurons of the RVLM. We will also test the possibility that vasopressin-containing pathways to RVLM neurons attenuate baroreceptor reflex control of sympathetic nerve activity. The results of these studies will define central neural pathways and mechanisms by which the brain renin angiotensin system can contribute to impaired baroreceptor reflex function and augmented activity of the sympathetic nervous system. By conducting these experiments in Ren-2 TG rats we will better assess the role of the brain renin angiotensin system on central neural control of cardiovascular function because key components of the renin angiotensin system (i.e. renin and angiotensin peptides) are over- expressed in this model.

这个项目将检验两个假设。 首先，血管流出 Ren-2转基因小鼠延髓头端腹外侧区（RVLM）神经元 (TG)含血管紧张素和加压素的 途径。 第二，血管紧张素和加压素输入到心血管 孤束核（nTS）和RVLM的神经元衰减 压力感受性反射控制血压和增强交感神经 TG大鼠的神经活动。 为了验证这些假设，我们提出了 具体目标。 1. 描述一下脑干和下丘脑 提供含血管紧张素或加压素的核 投射到RVLM的前交感神经元。 逆行径 追踪和免疫细胞化学技术将被用来确定这些 神经解剖学通路 这些实验的结果将提供 神经解剖学的基础来解释生理和 具有以下特定目的的神经药理学实验。 2. 证明了含血管紧张素的途径，以nTS和RVLM 减弱心率和交感神经活动的压力反射控制 TG大鼠。 负责血管紧张素II这种作用的受体亚型 或其它Ang肽将通过使用受体亚型 选择性拮抗剂 我们还将证明血管紧张素- 包含通向RVLM的通路导致交感神经流出增强 TG大鼠。 3.证明含有加压素的通路， nTS和RVLM有助于TG大鼠交感神经流出增加。 具体来说，我们将试图表明， nTS通路减弱正常的压力感受性反射功能， 含有加压素的RVLM通路提供兴奋性驱动， RVLM的前交感神经元。 我们还将测试 RVLM神经元的加压素通路减弱 交感神经活动的压力感受器反射控制。 结果 这些研究将定义中枢神经通路和机制， 大脑中的肾素血管紧张素系统会导致 压力感受器反射功能和交感神经活性增强 神经系统 通过在Ren-2 TG大鼠中进行这些实验，我们将 更好地评估脑肾素血管紧张素系统对中枢神经系统的作用， 心血管功能的神经控制，因为 肾素血管紧张素系统（即，肾素和血管紧张素肽）过度- 在这个模型中表示。