CENTRAL CONTROL OF SODIUM AND CARDIOVASCULAR HEMOSTASIS

本研究项目的长期目标是定义CNS 调节心血管血流动力学的神经递质系统。 压力反射是控制血压的重要中枢系统 并且受到大脑中多个部位的调节。灵敏度 压力感受器反射在许多实验和/或实验中是不稳定的和改变的。 病理条件。例如，压力反射重置在 高血压、充血性心力衰竭和CNS高渗期间。 精确的大脑部位和神经递质系统控制着 压力感受器反射功能尚未被表征。这些研究将定义 两个中枢神经系统的作用，前腹侧第三脑室（AV 3V）和 Broca对角带（DBB），和两种神经递质， 去甲肾上腺素（NE）和血管紧张素II（AngII）控制压力感受性反射 灵敏度拟议的研究将测试假设，即AV 3V 和/或DBB含有降低压力反射敏感性的神经细胞体 在CNS高渗期间，刺激去甲肾上腺素能和/或 血管紧张素能机制具体目标将决定：1）如果细胞 介导压力反射敏感性的身体位于AV 3V和/或 DBB，2）如果AV 3V和DBB中的NE介导压力反射敏感性降低 3）如果血管紧张素II在AV 3V和DBB介导下降低， 压力感受性反射对CNS高渗的敏感性，以及4）如果血管紧张素II和NE 在AV 3V和DBB中相互作用以降低压力反射敏感性。这些 通过测量血压的变化来实现特定的目的， 心率和腰、肾、肾上腺和内脏神经活动 在刺激压力感受器传入纤维期间的交感神经 （主动脉减压神经）和CNS微量注射神经兴奋性 药剂、神经毒素和/或特定药理学激动剂，以及 拮抗剂进入AV 3V和DBB。此外，体内微透析和 放射酶测定将用于评价NE释放和c-Fos 用于确定激活神经分布的免疫反应性 细胞在压力感受器传入刺激期间。 这些研究的结果将有助于实现 这个研究项目通过描述中枢神经系统和神经递质 参与心血管调节和血液压力反射控制 血压、心率和交感神经系统活动。 这些 研究将增加我们对中枢机制的理解， 调节压力反射敏感性和中枢神经系统对 压力反射重置

The long term objectives of this research project are to define the CNS sites and neurotransmitter systems regulating cardiovascular hemodynamics. The baroreflex is an important central system controlling blood pressure and is modulated by a number of sites in the brain. Sensitivity of the baroreflex is labile and altered in a number of experimental and/or pathological conditions. For example, baroreflex resetting is evident in hypertension, congestive heart failure, and during CNS hyperosmolality. The precise brain sites and neurotransmitter systems controlling baroreflex function have not been characterized. These studies will define the role of two CNS sites, the anteroventral third ventricle (AV3V) and the diagonal band of Broca (DBB), and two neurotransmitters, norepinephrine (NE) and angiotensin II (ang II) in control of baroreflex sensitivity. The proposed research will test the hypothesis that the AV3V and/or DBB contain nerve cell bodies which decrease baroreflex sensitivity during CNS hyperosmolality by stimulation of noradrenergic and/or angiotensinergic mechanisms. The Specific Aims will determine; 1) if cell bodies mediating baroreflex sensitivity are located in the AV3V and/or the DBB, 2) if NE in the AV3V and DBB mediate decreased baroreflex sensitivity to CNS hyperosmolality, 3) if ang II in the AV3V and DBB mediate decreased baroreflex sensitivity to CNS hyperosmolality, and 4) if ang II and NE interact in the AV3V and DBB to decreased baroreflex sensitivity. These specific aims will be achieved by measuring changes in blood pressure, heart rate, and nerve activity in lumbar, renal, adrenal, and splanchnic sympathetic nerves during stimulation of baroreceptor afferent fibers (aortic depressor nerve) and CNS microinjection of neural excitatory agents, neurotoxins, and/or specific pharmacological agonists and antagonists into the AV3V and DBB. In addition, in vivo microdialysis and radioenzymatic assay will be used to evaluate NE release, and c-Fos immunoreactivity used to determine the distribution of activated nerve cell is during baroreceptor afferent stimulation. Results from these studies will contribute to the long term objectives of this research project by characterizing CNS sites and neurotransmitters involved in cardiovascular regulation and baroreflex control of blood pressure, heart rate, and sympathetic nervous system activity. These studies will increase our understanding of central mechanisms which modulate baroreflex sensitivity and the contribution of the CNS to baroreflex resetting.