NTS Adenosine Receptors in Cardiovascular Control

描述（由申请人提供）：孤束核（NTS）是一种 延髓背侧的主要整合部位，用于处理内脏感觉 信息参与心血管控制和反射协调 自主反应模式NTS包含丰富的词汇， 神经递质/神经调质介导和调节NTS整合 其中腺苷强烈地参与了 控制自主神经活动，从而控制心血管 功能NTS内的腺苷水平随生理和病理变化而变化。 病理生理状态（例如，缺血、肿胀性出血、高血压） 最近的研究表明， 强烈支持的概念，腺苷发挥神经调节作用， NTS的自主控制机制。然而，几乎所有以前的 关于腺苷作用的研究仅限于 在细胞水平上的影响，或仅观察全球心血管 反应（例如动脉压和心率的变化）。只要 心血管控制是一个高度整合的过程， 生理和病理生理环境的区域变异性，我们 实验室结合了显微注射的强大方法， 大量的物质进入离散的脑干区域， 外周心血管器械，以开发独特的动物模型， 探讨孤束核调节心血管控制的机制 利用“最先进”的方法和分析技术。研究 本提案中所述的重点是确定功能重要性 和传出机制，其中腺苷在NTS内起作用以介导和 改变心血管系统的综合控制。此外，研究 建议中所描述的也旨在确定 腺苷受体亚型对压力和化学敏感细胞活性的影响 在NTS中。这些研究将大大增加我们对 在细胞水平上确定的过程的功能重要性， 心血管控制机制的综合协调， 新的药理学方法的发展，以治疗改变 中枢神经控制心血管功能。

DESCRIPTION (provided by applicant): The nucleus tractus solitarius (NTS) is a major integrative site in the dorsal medulla for processing viscerosensory information involved in cardiovascular control and the reflex coordination of autonomic response patterns. The NTS contains a rich vocabulary of neurotransmitters/neuromodulators mediating and modulating NTS integration among which adenosine has been strongly implicated in participating in the control of autonomic nerve activity and hence control of cardiovascular function. Adenosine levels within the NTS vary with both physiological and pathophysiological states (e.g. ischemia, hypotensive hemorrhage, high gravitational stress) and acting via adenosine P1 purinoceptors, recent studies strongly support the concept that adenosine plays a neuromodulatory role in the mechanisms of autonomic control by the NTS. However, nearly all previous studies regarding the actions of adenosine were restricted to either the effects at the cellular level or to observing only global cardiovascular responses (e.g. changes in arterial pressure and heart rate). Inasmuch as cardiovascular control is a highly integrative process and demonstrates marked regional variability in both physiological and pathophysiological settings, our laboratory has combined the powerful approaches of microinjection of very small quantities of substances into discrete brainstem areas with sophisticated peripheral cardiovascular instrumentation to develop a unique animal model to investigate the mechanisms of modulation of cardiovascular control by the NTS utilizing "state-of-the-art" methodologies and analytical techniques. Studies described in this proposal are focused on determining the functional importance and efferent mechanisms whereby adenosine acts within the NTS to mediate and modify integrative control of the cardiovascular system. Furthermore, studies described in the proposal are also designed to determine the effects of adenosine receptor subtypes on the activity of baro- and chemo-sensitive cells within the NTS. These studies will significantly increase our understanding of the functional importance of processes identified at the cellular level in the integrative coordination of cardiovascular control mechanisms and may aid in the development of new pharmacological approaches to the treatment of alter central neural control of cardiovascular function.