REGULATION OF MUSCLE BLOOD FLOW IN OLD AGE

本申请的目的是测试假设，即人类衰老改变了对活跃骨骼的血流调节， 全身运动时的骨骼肌。支持这一假设的有力证据来自于我们最近的发现，尽管老年人与年轻人的心输出量和腿部肌肉质量相似，但在次最大踏车测力计中腿部血流量减少。为了确定骨骼肌灌注持续时间的减少是否是衰老的必然结果，并阐明所涉及的机制，我们将讨论以下具体目标：1）运动期间主动肌肉血流量是否受年龄，性别或慢性体力活动的影响？2)与年轻受试者相比，老年受试者在次极量运动期间呼吸功（吸入HeO 2）的急性减少是否在更大程度上增加了主动肌血流量，如果是，如何增加？3)是否有证据表明运动时活性骨骼肌交感神经血管收缩与年龄相关，如果是，是否与肌纤维类型（针吸活检）的差异有关？4)有氧运动训练计划是否能改变年龄对腿部运动充血和血管舒张反应的影响？ 将通过在健康年轻（20 -30岁）和老年（60-75岁）男性和女性中进行分级腿部踏车测力计期间测量腿部血流量（股静脉热稀释法）、腿部去甲肾上腺素溢出、动脉压和心输出量（乙炔摄取）来研究这些问题。还将评估腿部肌肉质量（DEXA）和腿部血管舒张剂对局部给予哌唑嗪（目的3）和内皮依赖性和非依赖性激动剂（ACh、NTP、罂粟碱，目的4）的反应，作为年龄的函数。我们假设，正常老化与动态运动过程中主动肌肉血管舒张减少有关，这是由于呼吸肌血流需求增加，腿部交感神经血管收缩增强，呼吸肌血流需求受损，腿部交感神经血管收缩增强，内皮依赖性血管舒张受损。这些调查应大大有助于我们了解身体功能能力的下降和老年人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.