REACTIVE OXYGEN SPECIES AND VASCULAR O2 SENSING

活性氧和血管 O2 传感

• 批准号: 6391212
• 负责人: Michael S Wolin
• 金额: $ 27.39万
• 依托单位: NEW YORK MEDICAL COLLEGE
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-09-30 至 2004-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6391212
• 关键词: animal tissue; biological signal transduction; blood vessels; coronary artery; free radical oxygen; hypoxia; nitric oxide; oxygen tension; pulmonary artery; vascular endothelium; vascular smooth muscle

The long range goals of the studies described in this application are to elucidate how acute exposure to intermittent hypoxia-reoxygenation influences signaling mechanisms that control coronary and pulmonary vascular function. This laboratory has elucidated many aspects of how reactive oxygen species (ROS) and nitric oxide-derived species (RNS) interact with signaling systems which regulate processes that control vascular contraction and relaxation, and tissue respiratory processes, with an emphasis on how these mechanisms could function in responses elicited by changes in oxygen tension. It is hypothesized that ROS and RNS have important roles in the early modifications of vascular function caused by acute exposure to intermittent hypoxia. Thus, the overall goals of this project are to elucidate the roles of ROS and RNS in the initial alterations of vascular signaling mechanisms caused by exposure to intermittent hypoxia-reoxygenation that control the function of bovine coronary and pulmonary arteries. The first aim focuses on determining how intermittent hypoxia-reoxygenation alters signaling mechanisms that control bovine coronary and pulmonary arterial smooth muscle contractile function. The second aim examines how intermittent hypoxia-reoxygenation alters endothelium-derived signaling mechanisms that regulate coronary and pulmonary arterial function in large vessel and microvascular preparations. The third aim studies how intermittent hypoxia-reoxygenation alters oxygen sensing signaling mechanisms that regulate coronary and pulmonary arterial function. These studies could provide fundamental information on how intermittent hypoxia contributes to the initial alterations in vascular function which could be important factors in the pathogenesis of vascular diseases associated with sleep apnea and related disorders.

本申请中描述的研究的长期目标是 阐明急性暴露于间歇性缺氧-复氧如何影响 控制冠状动脉和肺血管功能的信号机制。 这个实验室已经阐明了活性氧如何 (ROS)和一氧化氮衍生物质（RNS）与信号系统相互作用 其调节控制血管收缩和舒张的过程， 组织呼吸过程，重点是如何这些机制， 在由氧张力变化引起的反应中起作用。 是 假设ROS和RNS在早期修饰中起重要作用 急性暴露在间歇性缺氧中引起的血管功能的变化。因此，在本发明中， 本项目的总体目标是阐明活性氧和RNS在 血管信号传导机制的最初改变是由暴露于 间歇性缺氧-复氧对牛功能影响 冠状动脉和肺动脉。 第一个目标是确定如何 间歇性缺氧-复氧改变了 牛冠状动脉和肺动脉平滑肌收缩功能。 第二个目的是研究间歇性缺氧-复氧如何改变 调节冠状动脉和肺动脉的内皮源性信号传导机制 大血管和微血管制备中的动脉功能。 第三 目的是研究间歇性缺氧-复氧如何改变氧感 调节冠状动脉和肺动脉功能的信号机制。 这些研究可以提供基本信息， 缺氧有助于血管功能的初始改变， 可能是血管相关疾病发病的重要因素 睡眠呼吸暂停综合征及相关疾病