Neuron-specific targeting of arteries and veins in hypertension

高血压动脉和静脉的神经元特异性靶向

• 批准号: 8148068
• 负责人: DAVID L KREULEN
• 金额: $ 32.04万
• 依托单位: MICHIGAN STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-07-10 至 2013-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8148068
• 关键词: Abdomen; Acetates; Action Potentials; Animals; Arteries; Behavior; Bilateral; Blood Pressure; Blood Vessels; Brain; Cardiovascular system; Celiac ganglion; Cell Culture Techniques; Cessation of life; Characteristics; Chest; Contracts; Deoxycorticosterone; Diet; Disease; Electric Capacitance; Endothelin B Receptor; Endothelin-1; Enzyme Activation; Enzymes; Ganglia; Generations; Hand; Health; Heart; Heart Contractilities; Human; Hypertension; Individual; Inferior; Lead; Left; Mediating; Mesentery; Morbidity - disease rate; Myxoid cyst; Nerve; Nervous System Part; Nervous System Physiology; Neurons; Neurotransmitters; Norepinephrine; Organ; Oxidases; Pathway interactions; Peripheral; Production; Property; Rattus; Reactive Oxygen Species; Regulation; Resistance; Signal Transduction; Signaling Molecule; Sodium; Sodium Chloride; Spinal Cord; Splanchnic Circulation; Stress; Structure of stellate ganglion; Superoxides; Sympathetic Ganglia; Sympathetic Nervous System; System; Up-Regulation; Vascular Capacitance; Vasoconstrictor Agents; Veins; Venous; Water; base; constriction; heart innervation; hemodynamics; mesenteric vein; nerve supply; neurochemistry; neurotransmitter release; noradrenaline transporter; normotensive; novel; receptor; uptake

Sustained elevated blood pressure-hypertension is a prominent cause of morbidity and deaths throughout the world. Hypertension is associated with increased activity in the sympathetic nervous system resulting in constriction of blood vessels, increased heart contractility and retention of sodium and water. It is the central hypothesis of this project that veins and arteries are innervated by separate neurons in sympathetic ganglia and that alterations in properties of vein neurons contribute to venoconstriction in hypertension. In normotensive and DOCA-salt hypertensive rats we will compare the properties of identified arterial and venous neurons in the prevertebral sympathetic ganglia that innervate the splanchnic blood vessels and and determine their properties with respect to firing behavior, generation of reactive oxygen species and function of the norepinephrine uptake system. We also will compare the properties of prevertebral neurons to those in stellate ganglia that provide the sympathetic innervation to the heart and associated great vessels in the thorax. We will pursue the following specific aims. 1) Determine the localization and electrophysiologic characteristics of arterial and venous sympathetic neurons in the intact inferior mesenteric ganglion of the rat and characterize arterial and venous neurons in primary dissociated cell culture. 2) Determine the localization and regulation of ROS-generating enzymes within the arterial and venous neurons of celiac ganglia and within stellate ganglion neurons. 3) Determine the mechanisms of regulation of sympathetic neuron function by ETB receptors. 4) Compare the properties of celiac ganglion neurons (peripheral volume regulation) to those of stellate ganglion neurons (central volume regulation). Our long-term objective is to discover novel properties of the sympathetic nervous system that will be susceptible to treatment of human hypertension. LAY SUMMARY: High blood pressure is a major health problem. The sympathetic nervous system, the part of the nervous system that functions when the body is stressed, is hyperactive in hypertension. This overactivity is a cause of the disease and many of the bad effects that accompany it. This study tries to find out what malfunctions in the nerve cells that are outside the brain and spinal cord that innervate the arteries, veins and heart. We think that the nerves that innervate veins cause them to contract too much and this is one cause of high blood pressure. We hope to discover a treatment based on this idea.

血压持续升高——高血压是整个地区发病和死亡的一个主要原因 世界。高血压与交感神经系统活动增加有关，导致 血管收缩、心脏收缩力增强以及钠和水的潴留。它是中央 该项目的假设是静脉和动脉由交感神经节中单独的神经元支配 静脉神经元特性的改变导致高血压的静脉收缩。在 对于血压正常和 DOCA 盐高血压大鼠，我们将比较已识别的动脉和 椎前交感神经节中的静脉神经元支配内脏血管和 确定它们在燃烧行为、活性氧的产生和功能方面的特性 去甲肾上腺素摄取系统。我们还将比较椎前神经元与椎前神经元的特性 星状神经节为心脏和相关大血管提供交感神经支配 胸部。我们将追求以下具体目标。 1) 确定定位和电生理 大鼠完整肠系膜下神经节动静脉交感神经元的特征 并表征原代分离细胞培养物中的动脉和静脉神经元。 2）确定 腹腔动脉和静脉神经元内 ROS 生成酶的定位和调节 神经节和星状神经节神经元内。 3）确定交感神经的调节机制 神经元通过 ETB 受体发挥功能。 4）比较腹腔神经节神经元的特性（外周体积） 调节）到星状神经节神经元的调节（中枢容量调节）。我们的长期目标是 发现交感神经系统的新特性，这些特性将对人类的治疗敏感 高血压。简单总结：高血压是一个主要的健康问题。交感神经 系统，即神经系统中在身体受到压力时发挥作用的部分，在以下情况下会过度活跃 高血压。这种过度活动是导致这种疾病以及随之而来的许多不良影响的原因。这 研究试图找出大脑和脊髓外部的神经细胞出现哪些故障， 支配动脉、静脉和心脏。我们认为支配静脉的神经导致静脉收缩 太多，这是高血压的原因之一。我们希望找到一种基于这个想法的治疗方法。