NTS Purinoreceptor in Integrative Cardiovascular Control

描述（申请人摘要）：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 不同区域的自主反应模式。NTS包含丰富的 神经递质/神经调质介导和调节NTS的词汇 其中腺苷和ATP两者的整合强烈地牵涉到 自主神经活动的控制，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，局部缺血，弥漫性出血，高 重力应力）。最近的研究有力地支持了这一概念， 腺苷通过腺苷P1嘌呤受体起神经调节作用 NTS的自主控制机制。此外，几条线路 我们实验室和其他人的证据表明，ATP， 在P2 x嘌呤受体，作为一种快速传递物质，在NTS介导的 压力反射控制外周循环的机制。几乎所有 以前关于腺苷和ATP作用的研究仅限于 无论是在细胞水平上的影响， 心血管反应（例如，动脉压和心率的变化）。 由于心血管控制是一个高度整合的过程， 在生理和心理学方面显示出明显的区域差异， 病理生理学设置，我们的实验室结合了强大的 将极少量物质显微注射到 具有复杂外周心血管系统的离散脑干区 能够监测局部血管和传出神经的仪器 开发独特的动物模型，以研究 利用“最新技术水平”通过NTS调节心血管控制 方法和分析技术。本提案所述研究包括： 重点是确定功能的重要性和传出机制 其中腺苷和ATP在NTS内起作用，以介导和调节整合 控制心血管系统。这些研究将大大增加 我们对在第三次会议上确定的进程的功能重要性的理解， 细胞水平在心血管综合协调控制中的作用 可能有助于开发新的药理学方法， 治疗心血管功能的中枢神经控制改变。

DESCRIPTION (Applicant's abstract): The nucleus tractus solitarius (NTS) is a major integrative site in the dorsal medulla for processing viscerosensory information involved in cardiovascular control and reflex coordination of regionally distinct autonomic response patterns. The NTS contains a rich vocabulary of neurotransmitters/neuromodulators mediating and modulating NTS integration among which both adenosine and ATP have been strongly implicated 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). Recent studies strongly support the concept that adenosine, acting via adenosine P1 purinoceptors, plays a neuromodulatory role in the mechanisms of autonomic control by the NTS. In addition, several lines of evidence from our laboratory and by others have suggested that ATP, acting at P2x purinoceptors, serves as a fast transmitter substance in NTS-mediated mechanisms of baroreflex control of the peripheral circulation. Nearly all previous studies regarding the actions of adenosine and ATP 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 capable of monitoring regional vascular and efferent neural activities 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 and ATP act within the NTS to mediate and modify integrative control of the cardiovascular system. 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 altered central neural control of cardiovascular function.