Vagal afferent cell bodies as sensors of blood-borne factors

迷走神经传入细胞体作为血源性因子的传感器

• 批准号: 7878582
• 负责人: stephen john lewis
• 金额: $ 29.2万
• 依托单位: UNIVERSITY OF VIRGINIA
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-09-15 至 2011-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7878582
• 关键词: Action Potentials; Address; Affect; Afferent Neurons; Angiotensin II; Argipressin; Axon; Axonal Transport; Blood; Blood Circulation; Blood Pressure; Blood flow; Brain; Cardiopulmonary; Cardiovascular Physiology; Cardiovascular system; Cell Surface Receptors; Cell membrane; Cells; Chemicals; Clip; Complex; Conscious; Consensus; Deposition; Development; Diabetes Mellitus; Disease; Elements; Enzymes; Ganglia; Health; Heart; Human; Hypertension; Immunohistochemistry; In Vitro; Indium; Inflammation; Inflammatory; Internal carotid artery structure; Ion Channel; Kidney; Lung; Membrane Potentials; Methods; Microcirculation; Modeling; Molecular Weight; Morphology; Muscle Tonus; Myxoid cyst; Nature; Nerve; Nodose Ganglion; Nucleus solitarius; Pathway interactions; Peripheral; Physiological; Plasma; Play; Pressoreceptors; Presynaptic Terminals; Process; Proteins; Rattus; Reflex action; Regulation; Renin; Research Personnel; Role; Septic Shock; Series; Signal Transduction; Smooth Muscle; System; Techniques; Tissues; Vascular blood supply; afferent nerve; argipressin receptor; clinically relevant; functional status; ganglion cell; glossopharyngeal; hemodynamics; human disease; in vivo; insight; neuronal cell body; novel; occipital artery; prevent; programs; receptor; receptor binding; receptor function; response; sensor; transmission process

DESCRIPTION (provided by applicant): Vagal afferent nerves play vital roles in the "moment to moment" and "long-term" regulation of hemodynamic status. This project focuses on the unique nature of the occipital artery microvasculature in nodose ganglia and its importance to the regulation of vagal afferent activity and cardiovascular function. Our first hypothesis is that the occipital artery microvasculature lacks an effective "blood-ganglion barrier" in order for circulating factors to gain access to, and regulate the activity of, vagal afferent cell bodies in nodose ganglia via interactions with cell-surface receptors. Such a system would allow for the "moment to moment" regulation of centrally-directed action potentials in vagal afferents and transmission of afferent information into the brain. At present, there is no consensus as to how disease processes such as humorally-induced hypertension, diabetes and inflammatory states affect the synthesis and disposition of receptors in vagal afferent neurons. Our second hypothesis is that the unique functional morphology of the occipital artery-nodose ganglion complex allows sustained increases in blood-borne factors to alter the synthesis of receptors in vagal afferent cell bodies and therefore the net availability of these receptors for insertion into the plasma membranes of the cell bodies and for axonal transport to the peripheral and central afferent terminals. This would represent a novel "long-term" homeostatic mechanism that allows vagal afferents to effectively adapt to increased levels of factors that are detrimental to afferent and cardiovascular function. The major focus of our project is to determine the importance of the occipital artery-nodose ganglion complex in integrative cardiovascular physiology in control rats and in 2-kidney-1 clip (2K-1C) hypertensive rats, a clinically-relevant model of humoral (renin)-dependent hypertension. We will employ functional in vivo, and in vitro techniques, and receptor binding/immunohistochemistry methods in a comprehensive approach to addressing our specific aims, which are to characterize (1) the accessibility of blood-borne factors to vagal afferent cell bodies, (2) the receptor sub-types involved in the actions of key circulating factors on afferent cell bodies, (3) the temporal changes in the expression and function of receptors in vagal afferents of control and 2K-1C hypertensive rats, and (4) the effects of and receptor-subtypes by which circulating factors regulate smooth muscle tone in the occipital artery microvasculature of control and 2K-1C rats. In lay terms, the aim of this project is to determine whether the cell bodies of nerves that regulate blood pressure by sending signals into the brain are able to respond directly to chemicals in the blood. This unique response mechanism may be vital in helping the body to defend the cardiovascular system against disease states that threaten human health such as high blood pressure, inflammation and diabetes.

描述（由申请人提供）：迷走神经传入神经在血流动力学状态的“时刻”和“长期”调节中发挥着至关重要的作用。该项目重点研究结状神经节枕动脉微血管的独特性质及其对迷走神经传入活动和心血管功能调节的重要性。我们的第一个假设是枕动脉微血管系统缺乏有效的“血神经节屏障”，以便循环因子能够通过与细胞表面受体的相互作用进入结状神经节中的迷走神经传入细胞体并调节其活性。这样的系统将允许对迷走神经传入中的中央定向动作电位进行“时刻到时刻”调节，并将传入信息传输到大脑中。目前，对于体液诱发的高血压、糖尿病和炎症状态等疾病过程如何影响迷走神经传入神经元受体的合成和配置尚未达成共识。我们的第二个假设是，枕动脉-结状神经节复合体的独特功能形态允许血源性因子持续增加，从而改变迷走神经传入细胞体中受体的合成，从而改变这些受体插入质膜的净可用性细胞体的轴突运输到外周和中枢传入终端。这将代表一种新颖的“长期”稳态机制，使迷走神经传入有效地适应不利于传入和心血管功能的因素水平的增加。我们项目的主要重点是确定枕动脉-结节神经节复合体在对照大鼠和 2-kidney-1 Clip (2K-1C) 高血压大鼠（一种临床相关的体液模型）中综合心血管生理学中的重要性。肾素）依赖性高血压。我们将采用功能性体内和体外技术以及受体结合/免疫组织化学方法，以综合方法来实现我们的具体目标，这些目标是表征（1）血源性因子对迷走神经传入细胞体的可及性，（2 ) 参与关键循环因子对传入细胞体作用的受体亚型，(3) 对照组和 2K-1C 高血压大鼠迷走神经传入神经中受体表达和功能的时间变化， (4) 循环因子调节对照大鼠和 2K-1C 大鼠枕动脉微血管系统平滑肌张力的受体亚型的作用。通俗地说，该项目的目的是确定通过向大脑发送信号来调节血压的神经细胞体是否能够直接对血液中的化学物质做出反应。这种独特的反应机制可能对于帮助身体保护心血管系统免受高血压、炎症和糖尿病等威胁人类健康的疾病至关重要。

项目成果

Morphine has latent deleterious effects on the ventilatory responses to a hypoxic challenge.

吗啡对缺氧挑战的通气反应具有潜在的有害影响。

• DOI: 10.4236/ojmip.2013.34022
• 发表时间: 2013
• 期刊: Open journal of molecular and integrative physiology
• 作者: May,WalterJ;Gruber,RyanB;Discala,JosephF;Puskovic,Veljko;Henderson,Fraser;Palmer,LisaA;Lewis,StephenJ
• 通讯作者: Lewis,StephenJ

Occipital Artery Function during the Development of 2-Kidney, 1-Clip Hypertension in Rats.

• DOI: 10.1155/2014/659617
• 发表时间: 2014
• 期刊: International journal of vascular medicine
• 影响因子: 1.3
• 作者: Chelko SP;Schmiedt CW;Lewis TH;Robertson TP;Lewis SJ
• 通讯作者: Lewis SJ

Low-dose morphine elicits ventilatory excitant and depressant responses in conscious rats: Role of peripheral μ-opioid receptors.

低剂量吗啡在清醒大鼠中引起通气兴奋和抑制反应：外周μ阿片受体的作用。

• DOI: 10.4236/ojmip.2013.33017
• 发表时间: 2013
• 期刊: Open journal of molecular and integrative physiology
• 作者: Henderson,Fraser;May,WalterJ;Gruber,RyanB;Young,AlexP;Palmer,LisaA;Gaston,Benjamin;Lewis,StephenJ
• 通讯作者: Lewis,StephenJ

Morphine has latent deleterious effects on the ventilatory responses to a hypoxic-hypercapnic challenge.

吗啡对缺氧高碳酸血症的通气反应具有潜在的有害影响。

• DOI: 10.4236/ojmip.2013.33019
• 发表时间: 2013
• 期刊: Open journal of molecular and integrative physiology
• 作者: May,WalterJ;Henderson,Fraser;Gruber,RyanB;Discala,JosephF;Young,AlexP;Bates,JamesN;Palmer,LisaA;Lewis,StephenJ
• 通讯作者: Lewis,StephenJ