Neuron-specific targeting of arteries and veins in hypertension

持续高血压--高血压是导致疾病和死亡的主要原因。 整个世界。高血压与交感神经系统活动增加有关，导致 收缩血管，增加心脏的收缩能力以及钠和水的滞留。它是中央 这个项目的假设是，静脉和动脉由交感神经节中单独的神经元支配 而且，静脉神经元特性的改变有助于高血压患者的静脉收缩。在……里面 正常血压和DOCA-盐性高血压大鼠，我们将比较识别的动脉和 椎前交感神经节中的静脉神经元，支配内脏血管和 根据燃烧行为、活性氧物种的生成和功能来确定它们的性质 去甲肾上腺素摄取系统。我们还将比较椎前神经元的特性与 星状神经节为心脏和相关的大血管提供交感神经。 胸腔。我们将追求以下具体目标。1)确定定位和电生理 大鼠肠系膜下神经节内动、静脉交感神经元的特征 并在原代分离细胞培养中鉴定动脉和静脉神经元。2)确定 腹主动脉和静脉神经元内ROS产生酶的定位和调节 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)比较腹壁神经节神经元的特性(外周体积 对星状神经节神经元的影响(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。通俗易懂：高血压是一个主要的健康问题。同情性神经质 当身体受到压力时，神经系统中起作用的部分--系统--过度活跃。 高血压。这种过度活动是导致这种疾病及其带来的许多不良影响的原因之一。这 这项研究试图找出大脑和脊髓外的神经细胞中有什么故障 支配动脉、静脉和心脏。我们认为支配静脉的神经使它们收缩 摄入过多，这是导致高血压的原因之一。我们希望基于这一想法找到一种治疗方法。

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.