REGULATION OF MUSCLE BLOOD FLOW IN OLD AGE

老年肌肉血流的调节

• 批准号: 6631477
• 负责人: DAVID N PROCTOR
• 金额: $ 21.49万
• 依托单位: PENNSYLVANIA STATE UNIVERSITY, THE
• 依托单位国家: 美国
• 财政年份: 1999
• 资助国家: 美国
• 起止时间: 1999-09-30 至 2004-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6631477
• 关键词: acetylcholine; aerobic exercise; age difference; cardiac output; clinical research; exercise; fiber cell; fine needle aspiration; hemodynamics; human old age (65+); human subject; human therapy evaluation; leg; muscle pharmacology; nitroferricyanide; norepinephrine; photon absorptiometry; prazosin; reactive hyperemia; striated muscles; thermal blood flow measurement; vasoconstriction; vasodilation; young adult human (21-34)

The goal of this application is to test the hypothesis that human aging alters the regulation of blood flow to active skeletal Skeletal muscles during whole body exercise. Compelling evidence supporting this hypothesis comes from our recent finding that leg blood flow during submaximal cycle ergometry is reduced in older versus younger aerobically-trained men, despite similar cardiac output and leg muscle mass. To determine if reduced skeletal muscle perfusion duration exertion is an inevitable consequence of aging, and to clarify the mechanisms involved, we will address the following specific aims: 1) Is active muscle blood flow during exercise influenced by age, gender, or chronic physical activity? 2) Does an acute reduction in the work of breathing (inspired HeO2) during submaximal exercise augment active muscle blood flow to a greater extent in older compared to younger subjects and if so, how? 3) Is there evidence for an age-associated increase in sympathetic vasoconstriction in active skeletal muscle during exercise and if so, is this related to differences in muscle fiber type (needle biopsy)? 4) Does an aerobic exercise training program modify the effects of age on exercise hyperemia and vasodilator responsiveness in the leg? These questions will be investigated by measuring leg blood flow (femoral vein thermodilution), leg norepinephrine spillover, arterial pressure, and cardiac output (acetylene uptake) during graded leg cycle ergometry in healthy younger z920-30 years) and older (60-75 years) men and women. Leg muscle mass (DEXA) and leg vasodilator responses to local administration of prazosin (Aim 3) and endothelial-dependent and independent agonists (ACh, NTP, papavarine, Aim 4) will also be assessed as a function of age. We hypothesize that normal aging is associated with reduced active muscle vasodilation during dynamic exercise and that this is due to increased respiratory muscle blood flow demands, augmented sympathetic vasoconstriction in the legs, and impaired respiratory muscle blood flow demands, augmented sympathetic vasoconstriction in the legs, and impaired endothelium-dependent vasodilation. These investigations should contribute significantly to our understanding of the decline in physical functional capacity and increased incidence of chronic disease in older humans.

该应用的目的是检验以下假设：人类衰老会改变整个身体运动过程中血液流向活跃的骨骼骨骼肌的调节。支持这一假设的令人信服的证据来自我们最近的发现，即尽管心输出量相似，但在年轻的有氧运动中，在年龄较大的有氧运动和年轻的有氧训练男性和腿部肌肉质量中，腿部血流降低了。为了确定减少骨骼肌肉灌注持续时间的劳累是否是衰老的必然结果，并阐明所涉及的机制，我们将解决以下特定目标：1）在运动过程中受年龄，性别或慢性体育活动影响的运动过程中有活性肌肉流动吗？ 2）与年轻受试者相比，在年龄较大的情况下，在次最大运动过程中呼吸工作的急性减少（受启发的HEO2）会增加活跃的肌肉血流吗？ 3）是否有证据表明运动过程中活跃骨骼肌的交感神经血管收缩相关，如果是，这与肌肉纤维类型的差异有关（针头活检）是否有关？ 4）有氧运动训练计划是否改变了年龄对腿部运动充血和血管舒张器反应的影响？ 这些问题将通过在健康的年轻Z920-30年的分级腿周期内测量腿部血流（股静脉热稀释），腿部去甲肾上腺素溢出，动脉压和心脏输出（乙炔摄取）和男性和女性（60 - 75年）的男性和女性。腿部肌肉质量（DEXA）和腿部血管扩张剂对局部给药（AIM 3）和内皮依赖性和独立激动剂（ACH，NTP，Papavarine，AIM 4）的局部给药反应也将作为年龄的函数进行评估。我们假设正常的衰老与动态运动过程中的活性肌肉血管舒张降低有关，这是由于呼吸道肌肉血流的增加，腿部的交感神经血管收缩增加，呼吸道肌肉血流需求受损，腿部增强的交感神经血管受到增强的交感神经，腿部和受损害的Entopherepired Entothertedentententententententented Vasodialtation rentedented Vasodicationdeptationdeptationdeptationdeptationdeptationdeptationdatiented vasodielation。这些研究应为我们对身体功能能力下降的理解和慢性疾病的发病率增加而产生重大贡献。