ENDOTHELIUM AND VASCULAR FUNCTION

本计划项目资助续期申请描述了我们计划的研究 作为我们先前关于…的作用的项目的延续 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。该项目 领导者代表相关的研究学科，每个学科都将 有助于调查人员的合作努力。平凡的 项目的主题是多方面的作用和互动 在局部释放的内皮衍生介质中--即一氧化氮 氧、氧自由基和前列腺素--在调控中的作用 血管平滑肌功能、血管张力和实质细胞 大鼠、狗和人心脏和骨骼肌的代谢。这个 参与调查的人员一直处于这方面研究的前沿 预计由于协调一致的方案， 提出血管内皮细胞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可能扮演的角色， 疾病状态，如心力衰竭，将变得更加清晰。工程 1将研究活性氧物种的产生和 氧化剂-一氧化氮相互作用对正常冠状动脉的影响 从心力衰竭和运动模型中获得的血管和血管 训练。项目2将检查与病理生理学相关的 一氧化氮在衰竭心脏循环中的消失 以及这对冠脉血管调节和氧气的影响 心肌细胞的代谢。项目3将调查 心力衰竭时内皮细胞一氧化氮生成的丢失 心肌细胞的坏死性和凋亡性死亡及其代谢 活性氧导致心脏功能不全。项目4 将以研究剪切应力的机制为目标 小动脉依赖性扩张与内皮细胞的作用 微血管功能改变的调节介质 运动训练和心力衰竭。一个管理核心将支持 研究项目。这种多学科的方法来研究 血管内皮细胞对血管和实质功能的贡献 具有更好地理解循环系统的潜力 生理学以及各种疾病的发病机制和可能的治疗 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.