Aging, Endothelial Dysfunction, and Impaired Vascular Control During Exercise

运动过程中的衰老、内皮功能障碍和血管控制受损

• 批准号: 7143159
• 负责人: FRANK A DINENNO
• 金额: $ 5.99万
• 依托单位: COLORADO STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-08-15 至 2008-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7143159
• 关键词: age difference; aging; antioxidants; ascorbate; cardiovascular pharmacology; cardiovascular stress test; catheterization; clinical research; exercise tolerance; free radical scavengers; hand; heart failure; human old age (65+); human subject; muscle contraction; nitric oxide; oxidative stress; prostaglandins; quality of life; reactive hyperemia; vascular endothelium; young adult human (21-34)

DESCRIPTION (provided by applicant): PROJECT SUMMARY: Aerobic exercise capacity declines progressively with advancing age eventually leading to increased disability, loss of independence, and reduced quality of life in older adults. The overall goal of this research program is to investigate the mechanism(s) involved in the impaired control of muscle blood flow and vascular tone during dynamic exercise in aging humans. This proposal seeks to mechanistically-link oxidative stress-induced peripheral endothelial dysfunction with impaired vascular control during dynamic exercise in aging humans. The general concept is that age-associated increases in oxidative stress reduce endothelium-derived nitric oxide (NO) bioavailability and cause the production of cyclooxygenase-derived vasoconstrictor prostaglandins (PGs), thus impairing local vasodilator responses during exercise in older adults. To test our hypotheses we will address the following specific aims: (1) we will determine whether the impaired control of muscle blood flow and vascular tone observed during dynamic exercise in older adults is due to age-related impairments in endothelium-dependent vasodilation, and specifically, we will determine the independent and interactive contribution of NO and PGs to this impairment; (2) we will determine whether acute reductions in oxidative stress in older adults improves endothelial vasodilator function and therefore, improves muscle blood flow and local vasodilator responses during exercise. The methods employed to address these aims are state-of-the-art and involve local (intraarterial) administration of various study drugs during exercise to investigate the roles of NO, PGs, and oxidative stress in the control of muscle blood flow in young and older healthy humans. The findings from the proposed studies should provide unique insight into the regulation of muscle blood flow and vascular control during exercise in aging humans, and also could have significant implications for the understanding and treatment of exercise intolerance in diseased populations that also demonstrate endothelial dysfunction e.g., heart failure patients). RELEVANCE: Aging is associated with a reduced quality of life which is due, in part, to reductions in exercise capacity. The studies in this application are designed to understand the potential contribution of impaired blood vessel function to exercise intolerance in older adults, and will provide ideas on how to prevent or improve this function, thereby enhancing the quality of life of older adults.

描述（由申请人提供）： 项目摘要：随着年龄的增长，有氧运动能力逐渐下降，最终导致老年人残疾增加、独立性丧失和生活质量下降。该研究计划的总体目标是研究老年人动态运动期间肌肉血流和血管张力控制受损的机制。该提案旨在从机制上将氧化应激引起的外周内皮功能障碍与老年人动态运动期间血管控制受损联系起来。一般概念是，与年龄相关的氧化应激增加会降低内皮源性一氧化氮（NO）的生物利用度，并导致环氧合酶源性血管收缩前列腺素（PG）的产生，从而损害老年人运动期间的局部血管舒张反应。为了检验我们的假设，我们将实现以下具体目标：（1）我们将确定老年人动态运动期间观察到的肌肉血流和血管张力控制受损是否是由于内皮依赖性血管舒张的年龄相关损伤所致，以及具体来说，我们将确定 NO 和 PG 对这种损伤的独立和交互贡献； (2)我们将确定老年人氧化应激的急剧减少是否可以改善内皮血管舒张功能，从而改善运动期间的肌肉血流量和局部血管舒张反应。用于实现这些目标的方法是最先进的，涉及在运动期间局部（动脉内）施用各种研究药物，以研究 NO、PG 和氧化应激在控制年轻人和老年人肌肉血流中的作用。年长的健康人类。拟议研究的结果应该为老年人运动期间肌肉血流和血管控制的调节提供独特的见解，并且也可能对理解和治疗也表现出内皮功能障碍的患病人群的运动不耐症产生重大影响，例如，心力衰竭患者）。相关性：衰老与生活质量下降有关，部分原因是运动能力下降。本申请中的研究旨在了解血管功能受损对老年人运动不耐受的潜在影响，并将为如何预防或改善这种功能提供思路，从而提高老年人的生活质量。