Neurohumoral control of veins in hypertension

描述（由申请人提供）：高血压是中风、冠状动脉疾病、心力衰竭和慢性肾病发病和死亡的危险因素。 以往对高血压病理生理学的研究主要集中在肾脏和动脉的神经体液控制。 该计划项目资助的一个独特方面是集中在静脉和建议，有重要的差异存在于正常的静脉和动脉的神经体液控制和静脉的神经体液控制异常有助于高血压的病因。 内皮素-1（ET-1）和交感神经系统调节静脉张力，在醋酸脱氧皮质酮（DOCA）-盐高血压大鼠模型中，ET-1和交感神经系统活性增加。 因此，这些研究将使用DOCA-盐大鼠作为实验模型。 该项目的主要目标是表征ET-1、交感神经和超氧阴离子如何相互作用以改变静脉张力，并建立静脉调节在高血压发展和维持中的相对重要性。 有四个高度相关的项目。 项目1（高血压中静脉张力和血管容量的神经体液调节）将集中在体内静脉调节。 项目2（内皮素肽与高血压动脉和静脉中的交感神经传递）将研究高血压相关的交感神经传递到血管的体外变化。 项目3（高血压中交感神经对肠系膜动脉和静脉的差异控制）将重点关注控制动脉和静脉的交感神经的特定亚群以及这些神经的特性如何在高血压中改变。 项目4（高血压中动脉和静脉的信号传导机制）将研究动脉和静脉平滑肌细胞中受体偶联信号传导机制的差异，以及这些机制的变化如何导致高血压。 四个核心单位将支持这些项目。 核心A将为该计划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。

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.