Limb Neurovascular Control and Aging

肢体神经血管控制与衰老

• 批准号: 7447409
• 负责人: KEVIN D MONAHAN
• 金额: $ 11.33万
• 依托单位: PENNSYLVANIA STATE UNIV HERSHEY MED CTR
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-07-01 至 2011-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7447409
• 关键词: Address; Adrenergic Agents; Adrenergic Receptor; Age; Aging; Arts; Award; Blood Vessels; Blood flow; Cardiovascular system; Central venous pressure; Data; Development; Elderly; Extramural Activities; Funding; Future; Goals; Human; Hypovolemia; Individual; Institution; K-Series Research Career Programs; Leg; Limb structure; Lower Extremity; Measures; Mediator of activation protein; Medicine; Mentors; Methodology; Microdialysis; Mission; Muscle; National Research Service Awards; Nerve; Neurons; Norepinephrine; Organ; Outcome; Physiological; Recording of previous events; Regulation; Research; Research Personnel; Research Training; Resources; Rest; Scientist; Skeletal Muscle; Stress; Sympathetic Nervous System; Synapses; Techniques; Testing; Training; Ultrasonography; Upper arm; Vasoconstrictor Agents; adrenergic; career; college; desire; experience; in vivo; insight; interstitial; investigator training; member; peripheral blood; presynaptic; response; reuptake; uptake; young adult

DESCRIPTION (provided by applicant): The candidate's short-term goal is to obtain advanced research training to significantly expand his research capabilities. The long-term goal of the candidate is to determine the mechanisms underlying detrimental age-associated changes in neurocirculatory control in humans. The candidate has an established ability and commitment to performing biomedically significant aging research and has successfully obtained extramural funding (Individual NRSA). Members of the mentoring team have a strong history of performing high quality extramurally-supported aging research and of training investigators. The resources at the Penn State College of Medicine (host institution) are excellent. The research training plan involves aspects critical to the development of future independent investigators such as formal classwork training, training in the use of modern experimental techniques, presenting and disseminating research findings, direct mentoring, and interacting with established investigators. Studies outlined in this proposal will utilize direct recordings of arm and leg muscle sympathetic nerve activity (MSNA), interstitial norepinephrine concentrations [NE]i in skeletal muscle, and limb blood flow to integratively examine mechanisms underlying age- and limb-related differences in peripheral blood flow regulation during central hypovolemic stress in humans. The following hypotheses will be tested: 1) resting and central hypovolemia-induced increases in MSNA are similar in the arm and leg of older adults. However, increases in limb MSNA during central hypovolemia elicit blunted vasoconstrictor responses in both the arm and leg of older compared to younger adults. 2) [NE]i is greater in the arm than the leg at rest and during central hypovolemia in young adults. Moreover, both arm and leg [NE]i are greater in older adults at rest and during central hypovolemia compared to young adults. 3) The mechanisms underlying age- and limb-related differences in [NE]i involve modulators of synaptic norepinephrine levels (uptake 1), but not presynaptic alpha-2 adrenergic modulation of NE release.

描述（由申请人提供）：候选人的短期目标是获得高级研究培训，以显着扩展其研究能力。候选人的长期目标是确定人类神经循环控制中与年龄相关的有害变化的潜在机制。候选人具有进行具有生物医学意义的衰老研究的既定能力和承诺，并已成功获得校外资助（个人 NRSA）。指导团队的成员在进行高质量的外部支持的老龄化研究和培训研究人员方面有着悠久的历史。宾夕法尼亚州立大学医学院（主办机构）的资源非常好。研究培训计划涉及对未来独立研究者发展至关重要的方面，例如正式的课堂作业培训、使用现代实验技术的培训、展示和传播研究成果、直接指导以及与现有研究者的互动。该提案中概述的研究将利用直接记录手臂和腿部肌肉交感神经活动（MSNA）、骨骼肌中间质去甲肾上腺素浓度[NE]i以及肢体血流量来综合检查外周血中与年龄和肢体相关的差异的机制。人类中枢性低血容量应激期间的血流调节。将测试以下假设：1）静息和中枢血容量不足引起的 MSNA 增加在老年人的手臂和腿部中相似。然而，与年轻人相比，中枢性血容量不足期间肢体 MSNA 的增加会导致老年人手臂和腿部的血管收缩反应减弱。 2) 在年轻人休息时和中枢性血容量不足时，手臂中的 [NE]i 大于腿部。此外，与年轻人相比，老年人在休息时和中枢性血容量不足时，手臂和腿部的 [NE]i 更大。 3) [NE]i 中与年龄和肢体相关的差异的机制涉及突触去甲肾上腺素水平的调节剂（摄取 1），但不涉及 NE 释放的突触前 α-2 肾上腺素能调节。