Neurohumoral Control of Veins in Hypertension

描述(由申请人提供)： 高血压是世界各地一个重大的公共卫生问题，因为它是心血管和肾脏疾病的重要危险因素。大多数了解和治疗这种疾病的努力从逻辑上讲都集中在肾脏或动脉上。该计划项目的三个中心和互补的主题是：静脉在长期控制动脉血压中发挥重要作用；调节静脉平滑肌活动的神经体液机制与动脉的神经体液机制根本不同；静脉特有的神经体液调节异常是高血压病因学的重要组成部分。实现上述实验目标的总体战略将是利用单个项目研究人员的不同科学专业知识-从整体动物研究到分子方法-详细测试将交感神经系统、ET-1和活性氧类与控制毒液运动张力和血压联系起来的单一综合假说。我们将主要利用DOCA-SALT的大鼠高血压模型，致力于了解高血压的病因。项目1将使用包括血压、平均循环充盈压、心输出量和使用生物阻抗的液体容量分布在内的一系列全身测量来评估清醒大鼠的静脉功能。项目2的重点是静脉和动脉肾上腺素能神经传递的差异以及静脉对高血压的适应机制。项目3旨在比较正常血压大鼠和高血压大鼠体内针对动脉、静脉和心脏的交感神经元的特性，以及交感神经节中超氧化物和其他活性氧物种的产生和作用。项目4将通过研究ET受体在动脉和静脉中的不同工作方式来研究动脉和静脉的功能，为什么动脉和静脉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压力有不同的反应(适应或不同)。综述：高血压是人类的一大健康问题。许多科学家认为高血压的原因可以在肾脏或动脉的功能异常中找到。这个项目测试了这样一种想法，即静脉结构或功能的改变也可能导致高血压，而且使用影响静脉的药物治疗高血压是可能的。

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.