Neurohumoral control of venous capacitance in hypertension

动脉血压持续上升--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 通过调节总血量来调节肾脏。这个项目的中心假设是静脉有助于 通过主动重新分配来自高顺应性血管的血液来长期控制动脉血压 间隔(外周静脉，特别是内脏静脉)到顺应性较低的间隔(中央静脉， 心脏和动脉)。我们的目标是在完整清醒的动物身上展示神经体液机制 控制外周静脉直径(外周血管电容)会影响动脉压和 高血压的发展。我们将使用两种大鼠高血压模型：DOCA-SALT；以及一种新的模型 我们认为这主要是基于静脉收缩，即S6c诱导的高血压。我们将解决我们的 具有以下具体目的的中心假说。1)确定静脉收缩是否导致体液 三种互补方法在高血压发展过程中的体积再分配 评估清醒大鼠的血容量再分配。2)建立一个减少的机制 高血压患者的血管电容是交感神经活动增加(和/或释放 在内脏区域使用直接神经记录和区域去甲肾上腺素) 溢出方法。3)显示内脏区域的交感神经支配如何影响 通过检测血管电容和动脉压对慢性高血压发展的影响 内脏交感神经的失神经和降低内脏交感神经中升高的超氧化物水平 神经节使用基因转移的方法。4)确定静脉收缩最终如何导致 通过测试小动脉肌张力、大动脉顺应性和心脏压力对动脉压的影响 交感神经活性在S6c诱发高血压发病中的作用。我们的最终目标是找出 治疗人类高血压的新策略。通俗易懂：高血压是一种 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情况下找到 肾或动脉的功能。这个项目测试了这样一种想法，即改变静脉的结构或功能 可能会导致高血压，使用影响静脉的药物治疗高血压是可能的。

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.