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部位，中枢神经化学系统， 外周生理机制，调节 心血管系统 我实验室以前的研究， 其他人已经证明，电刺激特定的 下丘脑中的区域控制血管紧张素和区域 单个外周血管床的血管阻力。 这些 结果导致的假设，有一个离散的安排， 控制血管扩张的大脑区域的神经结构 周围器官系统的紧张度。 对这些先前的解释 研究是有限的，因为：1）只有电刺激， 测试2）仅测量局部血流量;和3） 没有直接评估效应机制。 要扩展以前的 调查结果和解决这些问题，拟议的具体目标 将确定：1）CNS部位; 2）CNS神经递质系统; 3） CNS神经通路;和4）外周效应器机制， 控制特定区域和微血管反应。 这些目标 将通过使用：CNS微刺激，显微注射， 和刀切;放射自显影;辣根过氧化物酶技术; 药理学试剂的中枢和外周给药; 局部血流的脉冲多普勒分析;以及活体内 显微镜 肠系膜、肾脏和 臀部循环和皮肤中的微血管反应， 肠和骨骼肌将进行比较， 和化学刺激的离散神经网站在 下丘脑以前参与调节区域性 血管阻力 将确定其他实验 神经递质和其他中枢神经系统部位。 最后， 外周效应器机制将通过评估 充满药理学作用的组织中的微血管反应 中枢神经系统刺激期间的阻断剂。 该项目涉及 直接定义大脑在心血管疾病中的作用， 内稳态，并将增加我们对相互作用的理解 中枢神经系统和外周效应机制之间的调节 局部和总外周阻力。

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.