INTEGRATIVE NEUROBIOLOGY OF CARDIOVASCULAR REGULATION

该计划项目更新的重点是综合神经生物学的 心血管调节。它代表了主要的科学 爱荷华州心血管研究中心自1971年以来的重点工作。的 高级基础科学家和临床科学家之间强有力的凝聚力互动 研究人员补充了创新的方向， 招募优秀的新科学家。工作范围从 细胞/分子生物学到综合神经科学;从基因转移 在培养的细胞到基因工程动物中， 从孤立的系统到人类的机械研究。有五大 项目，每个项目都有紧密相关的交互部件。“中央RAS和 心血管调节”定义了血管紧张素的中枢作用， 选择性靶向中心核进行基因转移，调节 基因表达、化学消融和细胞电生理学。 “CGRP对感觉输入的调节”是一项旨在探索 通过伤害性刺激激活三叉神经传入， 蛛网膜下腔出血（SAH）。CGRP表达的变化可能 介导对疼痛的自主神经反应和破坏性的 血管痉挛的SAH，并持有治疗基因转移的承诺。在 《瘦素与中枢自主驱动》的重点是瘦素的作用， 在下丘脑的水平，在传导交感神经的激活 途径。肥胖症遗传模型的可用性和 汇集了各种科学专业知识，提供了一个独特的机会， 为了阐明瘦素与肾上腺素的相互作用，并将这项工作扩展到 肥胖的人类我们在压力感受器激活机制方面的经验 对离子通道的生物学和生物物理学的新兴趣将是 机械感觉和兴奋的细胞/分子机制 压力感受器神经元“四个独立但相互关联的部分将继续 ENaC/退化蛋白家族成员是BR传感器的概念，以及 蛋氨酸氧化还原在BR的调节中很重要， 离子通道通过自分泌因子。这些都是新颖而重要的概念。 “亚硝酰基因子和神经血管控制”扩展了正在进行的工作， 孤束核中多巴胺能和一氧化氮能神经元之间的相互作用， 这影响了压力感受器反射的中枢调节， 高血压和衰老。第二部分讨论了一个新的假设， 亚硝酰基因子在神经-内皮-血管 界面是调节血管张力主要机制。 基本核心职能将在以下领域支持这些项目： “成像”、“转基因动物”和“载体介导的基因转移"。“那 记录生产力、创造性互动、创新概念 和国家的最先进的方法承诺的最佳实现， 这项工作的科学成果将远远大于 组件。

This Program Project renewal focuses on Integrative Neurobiology of Cardiovascular Regulation. It has represented the major scientific emphasis of the Cardiovascular Research Center at Iowa since 1971. The strong cohesive interactions between senior basic scientists and clinical investigators is complemented by innovative directions with the recruitment of outstanding new scientists. The scope extends from work in cellular/molecular biology to integrative neuroscience; from gene transfer in cultured cells to genetically engineered animals; and from studies in isolated systems to mechanistic research in humans. There are five major Projects, each with tightly related interactive Parts. "Central RAS and Cardiovascular Regulation" defines the central action of angiotensin by selective targeting of central nuclei for gene transfer, regulation of gene expression, chemical ablation and cellular electrophysiology. "Modulation of Sensory Inputs by CGRP" is a coordinated effort to explore the activation of trigeminal afferents by nociceptive stimuli and subarachnoid hemorrhage (SAH). Changes in the expression of CGRP may mediate the disabling autonomic responses to pain and the devastating vasospasm in SAH, and hold the promise of therapeutic gene transfer. In "Leptin and Central Autonomic Drive" the focus is on the effect of leptin, at the level of hypothalamus, in transducing the activation of sympathetic pathways. The availability of genetic models of obesity and the convergence of diverse scientific expertise, provide a unique opportunity to clarify the autonomic-leptin interaction, and to extend the work to obese humans. Our experience in the mechanisms of baroceptor activation and new interests in the biology and biophysics of ion channels will be merged on "Cellular/Molecular Mechanism of Mechanosensation and Excitation of Baroreceptor Neurons." Four separate but interrelated Parts will pursue the concepts that ENaC/degenerin family members are the BR sensors, and that methionine oxidation-reduction is important in the regulation of BR ion channels by autocrine factors. These are novel and important concepts. "Nitrosyl Factors and Neurovascular Control" Extends ongoing work on the interaction between glutamatergic and nitroxidergic neurons in the NTS, which influences the central mediation of the baroreflex often impaired in hypertension and aging. A second Part addresses the novel hypothesis that "preformed stores"of nitrosyl factors, at the neuro-endothelial-vascular interface, represent a major mechanism of regulation of vascular tone. Essential Core functions will support these projects in the areas of "Imaging," "Transgenic Animals," and "Vector-Mediated Gene Transfer." The tract record of productivity, creative interactions, innovative concepts and state-of-the-art approaches promise the optimal realization of the work whereby the scientific outcome will be far greater than the sum of the components.