REGULATION OF MUSCLE BLOOD FLOW IN OLD AGE

本应用程序的目的是测试人体衰老在全身运动过程中改变活跃骨骼肌血液流动调节的假设。支持这一假设的有力证据来自我们最近的发现，尽管心输出量和腿部肌肉量相似，但在次最大周期测量中，老年人的腿部血流量比年轻有氧训练的男性减少。为了确定骨骼肌灌注持续时间消耗减少是否是衰老的必然结果，并阐明其中的机制，我们将解决以下具体目标：1)运动期间活跃的肌肉血流量是否受到年龄、性别或慢性体育活动的影响？2)与年轻人相比，在次最大运动期间呼吸功的急性减少（激发HeO2）是否在更大程度上增加了老年人的活跃肌肉血流量，如果是，是如何增加的？3)是否有证据表明运动期间活动骨骼肌的交感血管收缩与年龄相关，如果有，这是否与肌纤维类型的差异有关（针活检）？4)有氧运动训练计划是否能改变年龄对运动性充血和腿部血管扩张剂反应的影响？这些问题将通过测量腿部血流（股静脉热稀释）、腿部去甲肾上腺素溢出、动脉压和心输出量（乙炔摄取）在分级腿周期测量中对健康的年轻（20-30岁）和老年（60-75岁）男性和女性进行调查。腿部肌肉质量（DEXA）和腿部血管扩张剂对局部给药哌唑嗪（Aim 3）和内皮依赖和独立激动剂（ACh， NTP, papavarine, Aim 4）的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中活跃肌肉血管舒张减少有关，这是由于呼吸肌血流需求增加，腿部交感血管收缩增强，呼吸肌血流需求受损，腿部交感血管收缩增强，内皮依赖性血管舒张受损。这些研究将有助于我们理解老年人身体功能能力的下降和慢性病发病率的增加。

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.