REGULATION OF MUSCLE BLOOD FLOW IN OLD AGE

这个应用程序的目的是检验这样一个假设，即在全身运动过程中，人类的衰老改变了流向活跃骨骼肌的血流调节。支持这一假说的令人信服的证据来自我们最近的发现，尽管心输出量和腿部肌肉质量相似，但年龄较大的有氧运动训练男性的腿部血流量在次极大循环测功术中减少。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，并阐明其中涉及的机制，我们将解决以下具体目标：1)运动中活跃的肌肉血流量是否受到年龄、性别或慢性体力活动的影响？2)在次极量运动中呼吸功的急剧减少(灵感中的HeO2)是否会在较年长的受试者中更大程度地增加活跃的肌肉血流量？如果是，如何增加？3)是否有证据表明运动中活跃的骨骼肌的交感血管收缩随年龄的增加而增加，如果是这样的话，这是否与肌肉纤维类型的差异(针吸活检)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扩张剂反应性的影响？这些问题将通过测量健康的年轻男性和女性(920-30岁)和老年(60-75岁)的腿部血流量(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)来研究。腿部肌肉重量(DEXA)和局部应用哌唑嗪(AIM 3)和内皮依赖性和非内皮依赖性激动剂(ACh、NTP、罂粟碱、AIM 4)的腿部血管扩张剂反应也将作为年龄的函数进行评估。我们假设，在动态运动中，正常衰老与活跃的肌肉血管扩张减少有关，这是由于呼吸肌肉血流需求增加，腿部交感血管收缩增强，呼吸肌肉血流需求减弱，腿部交感血管收缩增强，内皮依赖性血管扩张受损。这些研究应该有助于我们理解老年人身体机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.