Neuron-specific targeting of arteries and veins in hypertension

持续的高血压-高血压是一个突出的原因，发病率和死亡的整个 世界高血压与交感神经系统活动增加有关， 收缩血管，增加心脏收缩力和钠和水的保留。是中央 该项目假设静脉和动脉由交感神经节中独立的神经元支配 并且静脉神经元特性的改变有助于高血压中的静脉收缩。在 正常血压和DOCA-盐高血压大鼠，我们将比较鉴定的动脉和 支配内脏血管的椎前交感神经节中的静脉神经元，和 确定它们在燃烧行为、活性氧物质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脊椎前神经元与脊椎中神经元的特性。 星状神经节，为心脏和相关的大血管提供交感神经支配， 胸部。我们将努力实现以下具体目标。1)确定定位和电生理 大鼠肠系膜下神经节动、静脉交感神经元的特性 并在原代分离的细胞培养物中表征动脉和静脉神经元。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)确定交感神经调节的机制 神经元功能通过ETB受体。4)比较腹腔神经节神经元的性质（外周体积 调节）到星状神经节神经元的那些（中央体积调节）。我们长远的目标是 发现交感神经系统的新特性，这些特性对人类的治疗很敏感 高血压摘要：高血压是一个主要的健康问题。交感神经 当身体受到压力时，神经系统中起作用的那部分系统就会过度活跃， 高血压这种过度活动是导致这种疾病的原因，也是伴随这种疾病的许多不良影响的原因。 一项研究试图找出大脑和脊髓外的神经细胞中的什么功能障碍， 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 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。

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.