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: 7880117
• 负责人: Darren Patrick Casey
• 金额: $ 5.22万
• 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/7880117
• 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（由申请人提供）：骨骼肌血管床在缺氧和动态运动时表现出分级血管扩张和血流量升高。有趣的是，与人类在控制条件下的运动相比，运动和缺氧相结合会产生“代偿性”血管扩张反应和更大的充血反应。在低氧运动中代偿性血管舒张和维持收缩肌肉的氧气输送的机制尚不清楚。人们普遍认为腺苷在缺氧诱导的骨骼肌血管舒张中起主要作用，但在运动性充血时似乎不是必需的。在这种情况下，该应用解决了腺苷参与运动期间代偿性血管舒张反应的总体假设，解决了以下具体目标。首先，腺苷和一氧化氮是否为低氧运动时代偿性血管舒张所必需。其次，确定红细胞在低氧运动中释放的ATP对腺苷（ADO）介导的代偿性血管舒张的可能贡献。第三，尚不清楚衰老是否会减弱低氧运动时的代偿性血管舒张反应，或者低氧运动中促进血管舒张的机制是否与年轻人相同或不同。此外，这些目标将作为一个理想的博士后培训工具，代表了他目前的技能集的重要延伸和扩展，使用的方法是在赞助商的实验室中建立良好的。所提出的实验设计的优势在于，我们将研究人体低氧运动时循环控制的基本机制。这些实验结果将为人类骨骼肌血流的代谢调节提供重要的新信息。进行身体活动和锻炼的能力是或应该是日常生活的重要组成部分。为了进行运动，必须有足够的血液流向运动肌肉。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含量低的疾病或状况。J