Neurohumoral control of venous capacitance in hypertension

动脉血压的持续升高-即高血压-是发病率过高的主要原因， 世界各地的死亡率慢性动脉压水平被认为主要是由 肾通过调节总血容量。这个项目的中心假设是静脉 通过从高顺应性血管主动重新分配血液来长期控制动脉压 隔室（外周，特别是内脏静脉）到较低顺应性的隔室（中央静脉， 心脏和动脉）。我们的目标是在完整的有意识的动物中展示神经体液机制 控制外周静脉的直径（外周血管容量）影响动脉压和 高血压的发展。我们将在大鼠中使用两种高血压模型：DOCA-盐模型和一种新模型。 我们认为主要是基于静脉收缩，即S6 c诱导的高血压。我们将解决我们的 中心假设与以下具体目标。1)确定静脉收缩是否会导致体液 通过使用三种互补方法， 评估清醒大鼠的血容量再分布。2)建立一种机制， 高血压中的血管电容是交感神经活动增加（和/或交感神经的释放）。 使用直接神经记录和局部去甲肾上腺素 溢出方法3)显示内脏区域的交感神经支配如何影响 血管容量和动脉压，通过测试对高血压发展的影响， 内脏交感神经去神经，并降低内脏交感神经中升高的超氧化物水平 利用基因转移的方法。4)确定静脉收缩如何最终导致增加 通过测试小动脉肌源性张力、大动脉顺应性和心脏的影响， 交感神经活动对S6 c诱导的高血压的发展。我们的最终目标是找出 治疗人类高血压的新策略。高血压（hypertension）是一种常见的高血压病。 严重的人类健康问题。许多科学家认为高血压的原因可以在异常中找到 肾或动脉的功能。这个项目测试的想法，改变结构或功能的静脉也 可能导致高血压，并且可能使用影响静脉的药物来治疗高血压。

A sustained increase in arterial blood pressure-i.e. hypertension-is a major cause of excess morbidity and mortality around the world. Chronic arterial pressure levels are thought to be established primarily by the kidney through regulation of total blood volume. The central hypothesis of this project is that veins contribute to long-term control of arterial pressure by actively redistributing blood from high compliance vascular compartments (peripheral, particularly splanchnic veins) to compartments of lower compliance (central veins, heart and arteries). Our goal is to show in intact conscious animals how neurohumoral mechanisms controlling the diameter of peripheral veins (peripheral vascular capacitance) affect arterial pressure and the development of hypertension. We will use two models of hypertension in rats: DOCA-salt; and a new model that we believe is based primarily on venoconstriction, i.e. S6c-induced hypertension. We will address our central hypothesis with the following Specific Aims. 1) Determine if venoconstriction causes body fluid volume redistribution during the development of hypertension by using three complementary methods to assess blood volume redistribution in conscious rats. 2) Establish that one mechanism of decreased vascular capacitance in hypertension is increased sympathetic nerve activity (and/or release of norepinephrine) in the splanchnic region using both direct nerve recording and regional norepinephrine spillover methods. 3) Show how sympathetic innervation to the splanchnic region affects regulation of vascular capacitance and arterial pressure by testing the effects on hypertension development of chronic splanchnic sympathetic denervation, and decreasing elevated superoxide levels in splanchic sympathetic ganglia using gene transfer methods. 4) Determine how venoconstriction ultimately leads to increased arterial pressure by testing the influence of small artery myogenic tone, large artery compliance, and cardiac sympathetic activity on the development of S6c-induced hypertension. Our ultimate objective is to identify novel strategies for treating human hypertension. Lay Summary: High blood pressure (hypertension) is a major human health problem. Many scientists feel the causes of hypertension can be found in abnormal function of the kidney or arteries. This project tests the idea that altered structure or function of veins also may cause hypertension, and that it may be possible to treat hypertension using drugs that affect veins.