CENTRAL CONTROL OF SODIUM AND CARDIOVASCULAR HOMEOSTASIS

在过去的九年里，我的研究目标是 确定中枢神经系统的位置，中枢神经化学系统，以及 调节血压的外周生理机制 心血管系统。我实验室以前的研究和 其他人已经证明，电刺激是一种特定的 下丘脑的区域控制血管舒张性张力和局部 单个外周血管床的血管阻力。这些 结果导致了假设，即存在一个离散的排列 控制血管运动的大脑区域的神经结构 周围器官系统中的音调。对这些先前版本的解释 研究受到限制，因为：1)只有电刺激 测试2)仅测量局部血流量；3)存在 没有对效应器机构的直接评估。要延长上一个版本 调查结果并解决这些关切，拟议的具体目标 将确定：1)中枢神经系统部位；2)中枢神经递质系统；3) 中枢神经通路；以及4)外周效应机制 控制特定的局部和微血管反应。这些目标 将通过使用：中枢神经系统微刺激、微注射、 和刀伤；放射自显影；辣根过氧化物酶技术； 中枢性和外周性给药； 局部血流和活体内血流的脉冲多普勒分析 显微镜。肠系膜、肾脏和肾脏的局部血流 后肢循环和皮肤的微血管反应， 肠道和骨骼肌将在电刺激过程中进行比较 以及对大脑中离散神经部位的化学刺激 下丘脑先前参与了局部的调节 血管阻力。其他实验将会确定。 神经递质和其他中枢神经系统部位参与其中。最后， 将通过评估来测试外围效应器机制 药物渗入组织中的微血管反应 中枢神经系统刺激过程中的阻滞剂。该项目涉及 直接定义大脑在心血管疾病中的作用 动态平衡，并将增加我们对相互作用的理解 在中枢神经系统和外周调节效应机制之间 局部和整体外周阻力。

For the past nine years, the objectives of my research have been to identify the CNS sites, the central neurochemical systems, and the peripheral physiological mechanisms which regulate the cardiovascular system. Previous studies from my laboratory and others have demonstrated that electrical stimulation of specific regions in the hypothalamus controls vasomotor tone and regional vascular resistance in individual peripheral vascular beds. These results led to the hypothesis that there is a discrete arrangement of neural structures in this brain region that controls vasomotor tone in peripheral organ systems. Interpretation of these previous studies is limited since: 1) only electrical stimulation was tested 2) only regional blood flow was measured; and 3) there was no direct evaluation of effector mechanisms. To extend previous findings and address these concerns, the proposed Specific Aims will determine: 1) CNS sites; 2) CNS neurotransmitter systems; 3) CNS nerve pathways; and 4) the peripheral effector mechanisms which control specific regional and microvascular responses. These aims will be achieved by using: CNS microstimulation, microinjection, and knife cuts; autoradiography; horseradish peroxidase techniques; central and peripheral administration of pharmacological agents; pulsed Doppler analysis of regional blood flow; and intravital microscopy. Regional blood flow in the mesenteric, renal, and hindquarter circulations, and microvascular responses in skin, intestine and skeletal muscle will be compared during electrical and chemical stimulation of discrete neural sites in the hypothalamus previously implicated in the regulation of regional vascular resistance. Additional experiments will be determine neurotransmitters and other CNS sites involved. Finally, peripheral effector mechanisms will be tested by evaluating microvascular responses in tissue suffused with pharmacological blocking agents during CNS stimulation. This project relates directly to defining the role of the brain in cardiovascular homeostasis, and will add to our understanding of the interaction between the CNS and peripheral effector mechanisms which regulate regional and total peripheral resistance.