Neurohumoral control of veins in hypertension

高血压静脉的神经体液控制

• 批准号: 6901927
• 负责人: Gregory D Fink
• 金额: $ 172.31万
• 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 2008-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6901927
• 关键词: endothelin; hypertension; neuroregulation; superoxides; sympathetic nervous system; veins

DESCRIPTION (provided by applicant): Hypertension is a risk factor for morbidity and mortality due to stroke, coronary artery disease, heart failure and chronic renal disease. Previous efforts to understand the pathophysiology of hypertension focused on the kidney and neurohumoral control of arteries. A unique aspect of this program project grant is focused on veins and the proposal that there are important differences exist in the neurohumoral control of veins and arteries normally and that abnormalities in neurohumoral control of veins contribute to the etiology of hypertension. Endothelin-1 (ET-1) and the sympathetic nervous system control venomotor tone and ET-1 and sympathetic nervous system activity is increased in deoxycorticosterone acetate (DOCA)-salt rat model of hypertension. Therefore, these studies will use DOCA-salt rats as the experimental model. The major goals of the project are to characterize how ET-1, sympathetic nerves and superoxide anions interact to alter venomotor tone and establish the relative importance of venomotor regulation in the development and maintenance of hypertension. There are four highly inter-related projects. Project 1 (Neurohumoral regulation of venomotor tone and vascular capacitance in hypertension) will focus on venomotor regulation in vivo. Project 2 (Endothelin peptides and sympathetic neurotransmission in arteries and veins in hypertension) will study hypertension associated changes in sympathetic neurotransmission to blood vessels in vitro. Project 3 (Differential control of mesenteric arteries and veins by sympathetic nerves in hypertension) will focus on the specific subgroups of sympathetic nerves that control arteries and veins and how the properties of these nerves are altered in hypertension. Project 4 (Signaling mechanisms in artiers and veins in hypertension) will study differences in receptor coupled signaling mechanisms in arterial and venous smooth muscle cells and how changes in these mechanisms contribute to hypertension. Four core units will support these projects. Core A will provide administrative support and overall supervision of the program. Core B will provide hypertensive animals and animal care support. Core C will provide analytical resources and Core D will provide support for tissue culture and gene transfer studies.

描述(申请人提供)：高血压是中风、冠状动脉疾病、心力衰竭和慢性肾脏疾病引起的发病率和死亡率的危险因素。以前对高血压病理生理学的了解主要集中在肾脏和神经体液对动脉的控制上。该计划项目拨款的一个独特方面是关注静脉，并提出在正常情况下对静脉和动脉的神经体液控制存在重要差异，以及对静脉的神经体液控制的异常有助于高血压的病因。在脱氧皮质酮-醋酸酯(DOCA)-盐高血压大鼠模型中，内皮素-1(ET-1)和交感神经系统控制毒动张力，ET-1和交感神经系统活性增加。因此，这些研究将以DOCA-SALT大鼠为实验模型。该项目的主要目标是确定ET-1、交感神经和超氧阴离子如何相互作用来改变毒液运动张力，并确定毒液运动调节在高血压的发生和维持中的相对重要性。有四个高度相关的项目。项目1(高血压中毒液张力和血管电容的神经体液调节)将集中于体内毒液调节。项目2(高血压时动脉和静脉中的内毒素和交感神经传递)将在体外研究与高血压相关的交感神经传递到血管的变化。项目3(高血压中交感神经对肠系膜动脉和静脉的不同控制)将专注于控制动脉和静脉的交感神经的特定亚群，以及这些神经的性质在高血压中如何改变。项目4(高血压患者动脉和静脉中的信号机制)将研究动脉和静脉平滑肌细胞中受体偶联信号机制的差异，以及这些机制的变化如何导致高血压。四个核心单位将为这些项目提供支持。核心A将为该项目提供行政支持和全面监督。核心B将提供高血压动物和动物护理支持。核心C将提供分析资源，核心D将为组织培养和基因转移研究提供支持。