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）：骨骼肌血管床表现出对缺氧以及动态运动期间的血管舒张和血流升高。有趣的是，与人类对照条件下的运动相比，运动和缺氧的结合产生了“补偿性”血管扩张剂的反应和更大的高血压反应。尚不清楚造成补偿性血管舒张的机制并保持O2递送到收缩肌肉中的机制尚不清楚。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，但在运动充血期间似乎并不是强制性的。在这种情况下，该应用程序解决了腺苷通过解决以下特定目标来参与锻炼过程中的补偿性血管扩张响应的总体假设。首先，腺苷和一氧化氮在低氧运动过程中的补偿性血管舒张是否强。其次，确定在缺氧运动期间对腺苷（ADO）介导的补偿性血管造成的释放的ATP的可能贡献。第三，尚不清楚衰老在低氧运动过程中的补偿性血管扩张剂反应是否会使缺氧运动期间促进血管舒张的机制与年轻个体中的血管舒张相同或不同。此外，这些目标将成为支持者的理想博士后训练工具，并使用在赞助商实验室中建立的方法代表其当前技能的大量扩展和扩展。提出的实验设计的强度是，我们将研究人类低氧运动期间循环控制的基本机制。这些实验的结果将提供有关人类骨骼肌血流的代谢调节的重要新信息。进行体育锻炼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血液锻炼肌肉升高的因素以及这些因素如何受到低水平的氧气影响。我们还试图研究人类衰老的这些事件，因为老年人有时会有疾病或疾病，导致血液中的氧气水平较低。 j