Aging and Sympathetic Vasoconstriction: Rest vs Exercise

描述（由申请人提供）：候选人Frank a . Dinenno博士，是一名生理学家，目前由NIA的一名NRSA个人资助。Dinenno博士以前和现在的研究重点一直是交感神经对循环的控制，特别强调这些控制机制是如何通过人类年龄的增长和规律的身体活动来调节的。他的近期目标是获得新的研究和专业技能，以更好地准备和帮助他实现他的长期目标，即开发一个成功的独立的校外资助的研究项目，研究衰老和心血管功能。这个拟议的KO1应该为Dinenno博士提供必要的培训，以实现他的目标。职业发展计划：Dr. Dinenno的研究职业发展培训活动将包括(1)获得与拟议的研究计划相关和补充的新研究技能；(2)结构化的研究和专业技能相关活动。环境：Dinenno博士的培训环境将会非常出色。发起人（乔伊纳博士）和咨询导师从事生物医学研究，并由NIH资助。所有人都是在生物医学研究方面有成功指导经验的知名科学家，其中三人是衰老研究方面的专家。综合临床研究中心的支持将改善培训环境。研究：将解决以下具体目标：1)确定健康人在休息条件下，全腿α -肾上腺素能受体的反应性是否随着年龄的增长而降低，以及这是否是cq-或c2-肾上腺素能受体所独有的；(2)确定老年人在大肌肉动态运动中钝性肾上腺素能血管收缩的能力是否受损；(3)这种受损是否由于氧化应激升高介导的一氧化氮生物利用度的年龄相关性降低所致；(4)确定有规律的有氧运动是否能提高以前久坐不动的老年人在休息和运动时减弱交感血管收缩的能力。预期的结果将提供有关老年人休息和运动时交感神经控制循环的新信息，干预研究将提供有关老年人训练诱导的适应和外周循环控制的新信息。

DESCRIPTION (provided by applicant): Candidate: The candidate, Frank A. Dinenno, Ph.D., is a physiologist currently supported by an individual NRSA from NIA. Dr. Dinenno's previous and current research focus has been on sympathetic neural control of the circulation, with specific emphasis on how these control mechanisms are modulated by advancing age and regular physical activity in humans. His immediate goal is to acquire new research and professional skills to better prepare and help him achieve his long-term goal of developing a successful independent extramurally-funded research program on aging and cardiovascular function. This proposed KO1 should provide Dr. Dinenno the necessary training to achieve his goal. Career Development Plan: Dr. Dinenno's research career development training activities will consist of (1) acquiring new research skills associated with and complimentary to the proposed research plan; and (2) structured research- and professional skills-related activities. Environment: The environment for Dr. Dinenno's training will be outstanding. The Sponsor (Dr. Joyner) and consulting mentors are engaged in biomedical research and are extramurally-funded from NIH. All are established scientists with strong records of successful mentoring in biomedical research, three of the six are experts in aging research. Support from the General Clinical Research Center will enhance the training environment. Research: The following specific aims will be addressed: 1) to determine whether whole-leg alpha-adrenergic receptor responsiveness is reduced with age under resting conditions in healthy humans, and whether this is specific for cq- or c2-adrenergic receptors; (2) to determine whether the ability to blunt-adrenergic vasoconstriction during large muscle dynamic exercise is impaired in older adults and (3) whether this impairment is due to age-related reductions in nitric oxide bioavailability mediated via elevations in oxidative stress; and (4) to determine whether a program of regular aerobic exercise improves the ability of previously sedentary older adults to blunt sympathetic vasoconstriction at rest and during exercise. The expected results should yield new information regarding sympathetic neural control of the circulation at rest and during exercise in aging humans, and the intervention study should yield novel information about training-induced adaptations and peripheral circulatory control in older adults.