Neurohumoral Control of Veins in Hypertension

高血压静脉的神经体液控制

• 批准号: 7822278
• 负责人: Gregory D Fink
• 金额: $ 1.76万
• 依托单位: MICHIGAN STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-06-01 至 2010-10-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7822278
• 关键词: Neurohumoral; Control; Veins; Hypertension; Neurohumoral; Control; Veins; Hypertension

DESCRIPTION (provided by applicant): Hypertension is a significant public health concern around the world because it is an important risk factor for cardiovascular and renal disease. Most efforts to understand and treat this condition have focused logically on either the kidney or arteries. The three central and complementary themes of this Program Project are: veins play an important role in the long-term control of arterial pressure; neurohumoral mechanisms regulating venous smooth muscle activity are fundamentally different from those of arteries; and abnormalities in neurohumoral regulation specific to veins are a significant part of the etiology of hypertension. The overall strategy for achieving the experimental goals listed above will be to capitalize on the diverse scientific expertise of individual project investigators - from whole animal studies to molecular approaches - to test in detail a single integrated hypothesis linking the sympathetic nervous system, ET-1 and reactive oxygen species to the control of venomotor tone and blood pressure. We will focus our efforts on understanding the etiology of hypertension primarily using the DOCA-salt model of hypertension in rats. Project 1 will assess venous function in conscious rats using a number of whole body measures including blood pressure, mean circulatory filling pressure, cardiac output, and fluid volume distribution using bioimpedance. Project 2 focuses on differences in adrenergic neurotransmission in veins versus arteries and the adaptive mechanisms of veins to hypertension. Project 3 aims at comparing properties of sympathetic neurons targeting arteries, veins and the heart in normotensive and hypertensive rats, and the generation and effects of superoxide and other reactive oxygen species in sympathetic ganglia. Project 4 will investigate arterial vs venous function by examining how ET receptors operate differently in arteries versus veins, why arteries and veins have different reactive oxygen species metabolizing systems and why veins and arteries have a different response (adaptive or otherwise) to the stresses of 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.

描述（由申请人提供）： 高血压是世界上重要的公共卫生问题，因为它是心血管和肾脏疾病的重要危险因素。理解和治疗这种情况的大多数努力都集中在肾脏或动脉上。该计划项目的三个中心和互补主题是：静脉在长期控制动脉压中起重要作用；调节静脉平滑肌活性的神经肿瘤机制与动脉根本不同。静脉特定的神经肿瘤调节的异常是高血压病因的重要组成部分。实现上面列出的实验目标的总体策略将是利用单个项目研究者的多样化科学专业知识（从整个动物研究到分子方法），以详细测试一个将单一的综合假设与交感神经系统，ET -1和反应性氧与毒方法和血压的控制联系。我们将重点放在理解高血压的病因上，主要是使用大鼠高血压模型。项目1将使用许多全身措施，包括血压，平均循环填充压力，心输出量和流体体积分布，使用生物阻抗来评估有意识大鼠的静脉功能。项目2的重点是静脉与动脉中肾上腺素能神经传递的差异以及静脉对高血压的适应性机制。项目3的目的是比较靶向动脉，静脉和心脏正常和高血压大鼠的性质的特性，以及超氧化物和其他反应性氧在交感神经节中的产生和作用。项目4将通过检查ET受体在动脉与静脉的不同作用，研究动脉与静脉功能，为什么动脉和静脉为何具有不同的活性氧代谢系统，以及为什么静脉和动脉对高血压的应力有不同的反应（适应性或其他方式）。摘要摘要：高血压（高血压）是人类健康问题。许多科学家认为，在肾脏或动脉的异常功能中可以找到高血压的原因。该项目测试了静脉结构或功能改变的想法也可能导致高血压，并且可以使用影响静脉的药物治疗高血压。