Neurohumoral control of venous capacitance in hypertension

高血压静脉容量的神经体液控制

• 批准号: 8148062
• 负责人: Gregory D Fink
• 金额: $ 20.89万
• 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/8148062
• 关键词: Abdomen; Accounting; Acute; Address; Affect; Agonist; Animals; Aorta; Arteries; Atrial Natriuretic Factor; Biological Markers; Blood; Blood Circulation; Blood Pressure; Blood Vessels; Blood Volume; Blood flow; Body Fluids; Caliber; Cardiac; Cardiac Output; Cardiovascular system; Celiac Plexus; Celiac ganglion; Central Vein; Chest; Chronic; Conscious; Coronary artery; Development; Drug usage; Electric Capacitance; Endothelin; Endothelin B Receptor; Excision; Ganglionectomy; Gene Transfer; Goals; Health; Human; Hypertension; Infusion procedures; Kidney; Measurement; Measures; Methods; Modeling; Morbidity - disease rate; Nerve; Norepinephrine; Organ; Peripheral; Peripheral Resistance; Plasma; Rattus; Reactive Oxygen Species; Regulation; Renal function; Role; Scientist; Side; Smooth Muscle; Splanchnic Nerves; Structure; Superoxides; Sympathectomy; Sympathetic Ganglia; Testing; Vascular Capacitance; Vascular Smooth Muscle; Veins; Venous; base; constriction; electric impedance; indexing; mortality; nerve supply; neuronal cell body; novel strategies; pressure; sarafotoxin 6c; small hairpin RNA

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.

动脉血压持续升高，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 肾脏通过调节总血容量。该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压 间室（外周静脉，特别是内静脉）到顺应性较低的间室（中央静脉， 心脏和动脉）。我们的目标是在完整有意识的动物中展示神经体液机制如何 控制外周静脉的直径（外周血管容量）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-盐；和一个新模型 我们认为这主要是基于静脉收缩，即 S6c 引起的高血压。我们将解决我们的 具有以下具体目标的中心假设。 1) 确定静脉收缩是否导致体液增多 通过使用三种互补的方法来改变高血压发展过程中的容量重新分配 评估清醒大鼠的血容量重新分布。 2）建立一种减少的机制 高血压的血管容量是交感神经活动增加（和/或释放 去甲肾上腺素）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调节 通过测试对慢性高血压发展的影响来测量血管容量和动脉压 内脏交感神经去神经支配，并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方法。 4) 确定静脉收缩最终如何导致增加 通过测试小动脉肌原性张力、大动脉顺应性和心脏的影响来测量动脉压 交感神经活动对 S6c 诱导的高血压发展的影响。我们的最终目标是确定 治疗人类高血压的新策略。摘要：高血压（hypertension）是一种 重大人类健康问题。许多科学家认为高血压的原因可以在异常情况中找到 肾脏或动脉的功能。该项目测试了改变静脉结构或功能的想法 可能导致高血压，并且可以使用影响静脉的药物来治疗高血压。