ENDOTHELIUM AND VASCULAR FUNCTION

本计划项目补助金更新申请描述了我们计划的研究 作为我们以前关于角色的项目的延续， 血管内皮细胞在心血管功能调节中的作用 各种生理和病理生理状态。 项目 领导者代表相关的研究学科，每个学科将 有助于调查人员的合作努力。 共同 项目的主题是多方面的作用和相互作用， 在局部释放的内皮衍生介质中，即，硝酸 氧化物、氧自由基和野牡丹素--在调节 血管平滑肌功能、血管张力和实质细胞 在大鼠、狗和人的心脏和骨骼肌中的代谢。 的 参与的研究人员一直处于研究的前沿， 预计，由于协调计划的实施， 提出，内皮介质在血管生物学中的作用， 以及它们在运动训练引起的变化中的可能作用， 和疾病状态，如心力衰竭，将变得更加清晰。 项目 1将研究活性氧的产生和 氧化剂-一氧化氮相互作用对正常冠状动脉的影响 血管和从心力衰竭和运动模型获得的血管 训练 项目2将检查 一氧化氮从衰竭心脏的循环中消失 以及这对冠状动脉血管调节和氧气的影响 心肌细胞的代谢。 项目3将调查 在衰竭的心脏中内皮一氧化氮形成的损失， 坏死和凋亡的心肌细胞死亡和代谢 导致心室功能障碍的活性氧。 项目4 将以研究剪切应力的机理为目标 小动脉的依赖性扩张和内皮细胞的作用 调节微血管功能改变的介质 运动训练和心力衰竭 行政核心将支持 研究项目。 这种多学科的研究方法， 内皮细胞对血管和实质功能的贡献 有可能导致更好地了解循环系统 生理学以及发病机制，并可能，治疗各种 疾病状态。

This Program Project Grant renewal application describes studies we plan to perform as a continuation of our previous project on the role of vascular endothelial cells in the regulation of cardiovascular function in a variety of physiological and pathophysiological states. The project leaders represent related research disciplines, each of which will contribute to the collaborative efforts of the investigators. The common theme of the projects is the multifaceted role of and the interaction among the locally released, endothelium-derived mediators - i.e., nitric oxide, oxygen free radical species and prostaglandins - in the regulation of vascular smooth muscle functions, vascular tone and parenchymal cell metabolism in heart and skeletal muscle of rats, dogs and humans. The participating investigators have been in the forefront of research in this area and it is anticipated that, as a result of the coordinated program proposed, the role of endothelial mediators in blood vessel biology as well as their possible role in the changes evoked by exercise training, and disease states, such as heart failure, will become clearer. PROJECT 1 will study the production of reactive oxygen species and the consequences of oxidant-nitric oxide interactions in normal coronary vessels and vessels obtained from models of heart failure and exercise training. PROJECT 2 will examine the pathophysiologic relevance of the disappearance of nitric oxide from the circulation of the failing heart and the consequences of this on coronary vascular regulation and oxygen metabolism of cardiac myocytes. PROJECT 3 will investigate the effects of the loss of endothelial nitric oxide formation in the failing heart on necrotic and apoptotic myocyte cell death and on the metabolism of reactive oxygen species leading to ventricular dysfunction. PROJECT 4 will have as its goal the study of the mechanisms of shear stress dependent dilation of arterioles and the contribution of endothelial mediators to the altered regulation of microvascular function after exercise training and heart failure. An Administrative Core will support the research projects. This multidisciplinary approach to the study of the contribution of endothelial cells to vascular and parenchymal function holds the potential of leading to a better understanding of circulatory physiology as well as the pathogenesis and, possibly, therapy of a variety of disease states.