ROLE OF TISSUE ANGIOTENSINS IN THE MEDULLA OBLONGATA

这个项目将检验两个假设。第一，血管运动的外流 转Ren-2基因大鼠延髓吻侧腹外侧区神经元 含血管紧张素和加压素的大鼠(TG)增强 小路。第二，血管紧张素和加压素对心血管的输入 孤束核(NTS)和RVLm神经元的衰减 压力感受器反射控制血压和增强交感神经 TG大鼠的神经活动。为了检验这些假设，我们提出了 遵循特定的目标。1.描述脑干和下丘脑 提供含有血管紧张素或加压素的核 向RVLM的交感前神经元的投射。逆行束 将使用示踪和免疫细胞化学技术来定义这些 神经解剖路径。这些实验的结果将提供一种 神经解剖学基础为解释生理和 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NTS和RVLm通路 减弱压力感受性反射对心率和交感神经活动的控制 在TG大鼠中。血管紧张素Ⅱ这一作用的受体亚型 或其他Ang多肽将通过使用受体亚型来表征 选择性的拮抗剂。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加 在TG大鼠中。3.证明含有加压素的通路通向 NTS和RVLm促进TG大鼠交感神经外流。 具体地说，我们将试图证明含有加压素的 NTS的通路减弱正常压力感受性反射功能，而 通向RVLM的含有加压素的通路提供兴奋性驱动 RVLM的交感前神经元。我们还将测试这种可能性 通向RVLM神经元的含有加压素的通路减弱 压力感受器反射对交感神经活动的控制。结果是 这些研究将通过以下方式定义中枢神经通路和机制 大脑肾素血管紧张素系统可能对受损的 压力感受器反射功能与交感神经活动增强 神经系统。通过在Ren-2 TG大鼠身上进行这些实验，我们将 更好地评估大脑肾素血管紧张素系统在中枢神经系统中的作用 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- 在这个模型中表达。

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.