Role of Adenosine in Compensatory Dilation During Hypoxic Exercise

腺苷在缺氧运动期间代偿性扩张中的作用

• 批准号: 7668371
• 负责人: Darren Patrick Casey
• 金额: $ 5.01万
• 依托单位: MAYO CLINIC ROCHESTER
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-07-23 至 2011-07-22
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7668371
• 关键词: Address; Adenosine; Aging; Aminophylline; Attenuated; Blood; Blood flow; Contracts; Cystic Fibrosis; Dilator; Disease; Erythrocytes; Event; Exercise; Exhibits; Experimental Designs; Forearm; Goals; Human; Hyperemia; Hypoxia; Individual; Laboratories; Life; Mediating; Metabolic; Muscle; Nitric Oxide; Oxygen; Physical activity; Play; Purinergic P1 Receptors; Regulation; Role; Skeletal Muscle; Source; Testing; Vasodilation; Vasodilator Agents; contextual factors; cystic fibrosis patients; healthy aging; post-doctoral training; research study; response; skills; vascular bed

DESCRIPTION (provided by applicant): Skeletal muscle vascular beds exhibit a graded vasodilation and elevated blood flow in response to hypoxia as well as during dynamic exercise. Interestingly, the combination of exercise and hypoxia produces a "compensatory" vasodilator response and an even greater hyperemic response compared to exercise under control conditions in humans. The mechanisms responsible for the compensatory vasodilation and maintained O2 delivery to contracting muscles during exercise with hypoxia remain unclear. It is generally accepted that adenosine plays a major role in hypoxia-induced skeletal muscle vasodilation but does not appear to be obligatory during exercise hyperemia. In this context, this application addresses the overall hypothesis that adenosine participates in the compensatory vasodilator responses seen during exercise by addressing the following specific aims. First, whether adenosine and nitric oxide are obligatory for the compensatory vasodilation during hypoxic exercise. Second, determine the possible contribution of ATP released from erythrocytes during hypoxic exercise has on the adenosine(ADO) mediated compensatory vasodilaton. Third, it is not known if aging blunts the compensatory vasodilator response during hypoxic exercise or if the mechanisms that promote vasodilation during hypoxic exercise are the same or different than those in younger individuals. In addition, these aims will serve as an ideal postdoctoral training vehicle for the proponent and represent a significant extension and expansion of his current skill set using approaches that are well established in the sponsor's laboratory. The strength of the proposed experimental design is that we will study the basic mechanisms of circulatory control during hypoxic exercise in humans. The results of these experiments will provide important new information about the metabolic regulation of skeletal muscle blood flow in humans. The ability to perform physical activity and exercise are or should be essential components of everyday life. For exercise to be performed there must be adequate blood flow to the exercising muscles. This proposal seeks to study the factors that cause blood flow to rise in exercising muscles and how these factors might be influenced by low levels of oxygen. We also seek to study these events in aging humans because older humans sometimes have diseases or conditions that result in low levels of oxygen in the blood. J

描述（由申请方提供）：骨骼肌血管床表现出分级血管舒张和血流量升高，以响应缺氧以及动态运动。有趣的是，运动和缺氧的组合产生了“补偿性”血管扩张反应，并且与人类在控制条件下的运动相比，产生了甚至更大的充血反应。在低氧运动过程中，负责代偿性血管舒张和维持O2输送到收缩肌肉的机制尚不清楚。一般认为，腺苷在缺氧引起的骨骼肌血管舒张中起主要作用，但在运动充血期间似乎不是强制性的。在这种情况下，本申请通过解决以下具体目标来解决腺苷参与运动期间观察到的代偿性血管扩张反应的总体假设。第一，腺苷和一氧化氮是否是低氧运动时代偿性血管舒张的必要条件。第二，研究低氧运动时红细胞释放ATP对腺苷（ADO）介导的代偿性血管舒张的作用。第三，尚不清楚衰老是否会减弱低氧运动期间的代偿性血管舒张反应，或者低氧运动期间促进血管舒张的机制与年轻个体相同还是不同。此外，这些目标将作为一个理想的博士后培训工具的支持者，并代表了一个显着的延伸和扩展，他目前的技能集使用的方法是在赞助商的实验室建立良好。建议的实验设计的优势是，我们将研究在人体低氧运动循环控制的基本机制。这些实验的结果将提供有关人体骨骼肌血流代谢调节的重要新信息。进行身体活动和锻炼的能力是或应该是日常生活的基本组成部分。为了进行锻炼，必须有足够的血液流向锻炼的肌肉。该提案旨在研究导致运动肌肉血流量增加的因素以及这些因素如何受到低氧水平的影响。我们还试图研究老年人的这些事件，因为老年人有时会患有导致血液中氧气水平低的疾病或病症。J