Integrative Neurobiology of Cardiovascular Regulation

描述(由申请人提供)： 该项目的重点是心血管调节的综合神经生物学。自1971年以来，它一直代表着爱荷华州心血管研究中心的主要科学重点。这一竞争更新的优势，现在是它的第30个年头，基于其高级领导层的稳定性、生产力和凝聚力，以及将分子生物学与综合神经生物学和心血管疾病机制联系起来的持续努力。该应用程序有七个项目，比当前计划少了一个。七个项目中有三个涉及循环的中枢神经控制，两个研究压力感受器和心脏感觉传入的反射控制，两个研究神经血管机制。这三个中枢神经控制项目是：A.K.约翰逊关于抑郁症引起的心脏病发病率和死亡率惊人增加的机制的项目；Davisson/Sigmund关于大脑肾素-血管紧张素系统选择性区域和细胞激活的功能意义的项目；以及费尔德关于免疫系统激活(细胞因子)在心肌梗死-心力衰竭引起交感神经驱动增强的中枢神经系统作用的项目。这两个反射控制项目是：Abboud/Benson/Welsh关于压力感受器机械转导的分子决定因素以及心肌缺血和衰竭时心脏感觉传入的机械和质子敏感性的项目；以及Chapleau/Hoshi关于动脉粥样硬化和衰老中压力反射功能障碍的区别机制的项目。关于神经血管机制的两个项目是：Haynes/Mark关于交感神经激活在人类肥胖中的血管后果的项目，以及Russo/Faraci/Heistad的项目，该项目是对蛛网膜下腔出血中CGRP的重要工作的扩展，该工作探索了促进CGRP受体在脑血管三叉神经血管系统中表达的新的分子机制。除了管理核心，成像/免疫细胞化学核心以及转基因和载体核心已经为现有计划提供了宝贵的服务。技术方法是最先进的，动物模型建立得很好，工作是机械化的，概念是创新的。与抑郁症和心肌梗塞、心力衰竭、高血压、动脉粥样硬化、中风和肥胖症等病态和致命疾病的相关性是直接的。我们预计科学结果将远远大于各组成部分的总和。

DESCRIPTION (provided by applicant): The Program Project Grant focuses on Integrative Neurobiology of Cardiovascular Regulation. It has represented the major scientific emphasis of the Cardiovascular Research Center at Iowa since 1971. The strength of this competitive renewal, now it its 30th year is based on the stability, productivity and cohesion of its senior leadership and the continuous effort to link molecular biology to integrative neurobiology and mechanisms of cardiovascular disease. The application has seven projects one less than the current program. Three of the seven projects address the central neural control of the circulation, two examine the reflex control from baroreceptors and cardiac sensory afferents, and two examine neurovascular mechanisms. The three central neural control projects are: the project by A.K. Johnson on the mechanisms of the alarming increase in morbidity and mortality from cardiac disease associated with depression; the project by Davisson/Sigmund on the functional significance of the selective regional and cellular activation of the brain renin-angiotensin system; and the project by Felder on the CNS effects of immune system activation (cytokines) in myocardial infarction-heart failure causing increased sympathetic drive. The two reflex control projects are: the project by Abboud/Benson/Welsh on the molecular determinants of mechanotransduction in baroreceptors and mechano- and proton-sensitivity of cardiac sensory afferents in myocardial ischemia and failure; and the project by Chapleau/Hoshi on the differential mechanisms of baroreflex dysfunction in atherosclerosis and aging mediated by reactive oxygen species. The two projects on neurovascular mechanisms are: the project by Haynes/Mark on vascular consequences of sympathetic neural activation in human obesity, and the project by Russo/Faraci/Heistad which is an extension of the important work on CGRP in subarachnoid hemorrhage exploring novel molecular mechanisms for enhancing the expression of CGRP receptors in the trigeminovascular system of cerebral vessels. In addition to the Administration Core, the Imaging/Immunocytochemistry Core and the Transgenic and Vector Cores are already providing invaluable service to the existing programs. The technical approaches are state-of the-art, the animals models are well established, the work is mechanistic and the concepts are innovative. The relevance to morbid and fatal disease such as depression and myocardial infarction, heart failure, hypertension, atherosclerosis, stroke and obesity is direct. We expect the scientific outcome to be far greater than the sum of the components.