NTS Purinoreceptor in Integrative Cardiovascular Control

NTS 嘌呤受体在心血管综合控制中的应用

• 批准号: 6579955
• 负责人: Donal S O'Leary
• 金额: $ 6.93万
• 依托单位: WAYNE STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-03-01 至 2003-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6579955
• 关键词: adenosine; autonomic nervous system; cardiovascular function; laboratory rat; microinjections; neuroregulation; purinergic receptor; solitary tract nucleus

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.

描述（申请人的摘要）：核Tractus solitarius（NTS）是一个 背髓的主要整合位点处理内脏感 涉及心血管控制和反射协调的信息 区域不同的自主响应模式。 NTS包含一个富人 神经递质/神经调节剂的词汇介导和调节NTS 腺苷和ATP的整合都与 自主神经活动的控制，因此控制心血管 功能。 NTS内的腺苷水平随生理和 病理生理态（例如缺血，低血压出血，高 重力应力）。最近的研究强烈支持这样的概念 腺苷通过腺苷P1 Purinoceptor作用，扮演神经调节作用 在NTS的自主控制机制中。另外，几行 我们实验室和其他人的证据都建议ATP，代理 在P2X Purinoceptors，作为NTS介导的快速发射器物质 周围循环的压力反射控制机制。几乎全部 先前关于腺苷和ATP作用的研究仅限于 在细胞水平上的影响或仅观察全局 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综合的过程， 证明生理和 病理生理设置，我们的实验室结合了强大的 将非常少量物质的显微注射方法进入 离散的脑干区域，具有复杂的外周心血管 能够监测区域血管和发出神经的仪器 开发独特动物模型的活动以研究 NTS利用“最先进”对心血管控制的调节 方法和分析技术。该提议中描述的研究是 专注于确定功能重要性和传出机制 腺苷和ATP在NTS中起作用以调解和修改整合性 控制心血管系统。这些研究将大大增加 我们对在该过程中确定的过程的功能重要性的理解 心血管控制综合协调的细胞水平 机制，可能有助于开发新的药理学方法 治疗心血管功能改变中央神经控制的治疗。