HRT and Exercise Effects on Central Arterial Compliance

描述（由申请人提供）：候选人。候选人Kerrie L. 莫罗博士，是一位生理学家，目前由一个独立的NRSA支持。 从NIA。Moreau博士过去和现在的研究重点是物理 活动，衰老和心血管健康，特别是女性。她 近期目标是获得新的研究和专业技能，以帮助她 实现她的长期目标，发展一个成功的独立 一个由校外资助的老龄化研究项目KO 1开发项目 该计划应提供莫罗博士必要的培训，以实现她的 目标. 职业发展计划。Moreau博士的研究职业发展培训 活动包括：1）获得与研究相关的新技能， 互补于（例如，微阵列去表达分析）的建议， 研究计划; 2）有组织的活动，包括正式的课程工作; 出席和发表在期刊俱乐部，研讨会系列，和科学 会议;以及与她的指导团队的定期互动。 环境莫罗博士的训练环境应该是杰出的。 申办者和共同申办者道格拉斯·西尔斯博士和温迪·柯尔特博士都很好- 建立了外部资助的科学家与成功的记录， 指导生物医学老化研究。他们受到了几个人的称赞 咨询导师，他们将在培训的特定领域提供指导 计划其他从事老龄化研究的教师则致力于改善环境。 Research.一般目的是确定3的相对功效。 常用的激素替代疗法（HRT）方案，定期有氧运动 运动，以及HRT与运动相结合，以改善中枢神经系统 （颈动脉）动脉顺应性，相关的功能益处，以及 绝经后健康女性久坐雌激素缺乏的潜在机制 妇女一般的假设是，HRT和运动将，独立和 此外，改善动脉顺应性，这反过来又会导致 功能益处（例如，心迷走神经压力反射敏感性的改善 和左心室功能/结构），这些有利的适应 将部分通过交感神经张力的降低（仅HRT）和/或 减少氧化应激相关的血管内皮改善- 依赖性血管舒张张力。此外，激素的改善量 补充和运动的累加效应将不同HRT 养生法 一项2期安慰剂对照干预试验， 自主神经（如微神经造影）和心血管的最新测量 (e.g.,高分辨率超声检查）功能。的 预期结果应提供新的生理和临床信息 关于使用各种HRT方案和运动的主要 预防中心动脉顺应性随年龄和雌激素而降低 缺乏，相应的植物神经和心血管功能 好处，以及对所涉及的潜在机制的洞察。

DESCRIPTION (provided by applicant): Candidate. The candidate, Kerrie L. Moreau, Ph.D., is a physiologist currently supported by an individual NRSA from NIA. Dr. Moreau's past and current research focus has been on physical activity, aging, and cardiovascular health, particularly in women. Her immediate goal is to acquire new research and professional skills to help her achieve her long-term goal of developing a successful independent extramurally-funded research program in aging. The proposed KO1 development plan should provide Dr. Moreau with the necessary training to achieve her goal. Career Development Plan. Dr. Moreau's research career development training activities consist of: 1) acquiring new research skills associated with and complimentary to (e.g., micro array gone expression analysis) the proposed research plan; and 2) structured activities including formal course work; attendance and presentation at journal clubs, seminar series, and scientific meetings; and regular interactions with her mentoring team. Environment. The environment for Dr. Moreau's training should be outstanding. The Sponsor and Co-sponsor, Drs. Douglas Seals and Wendy Kohrt, are well- established extramurally-funded scientists with strong records of successful mentoring in biomedical aging research. They are complimented by several consulting mentors who will provide guidance in specific areas of the training plan. Other faculty in aging research enhance the environment. Research. The general aim will be to determine the relative efficacy of 3 commonly used Hormone Replacement Therapy (HRT) regimens, regular aerobic exercise, and the combination of HRT and exercise for improving central (carotid) arterial compliance, the associated functional benefits, and the underlying mechanisms in healthy sedentary estrogen-deficient postmenopausal women. The general hypothesis is that HRT and exercise will, independently and additively, improve arterial compliance which will, in turn, result in functional benefits (e.g., improvements in cardiovagal baroreflex sensitivity and left-ventricular function/structure), and that these favorable adaptations will be mediated in part by a decrease in sympathetic tone (HRT only) and/or a reduced oxidative stress-associated improvement in vascular endothelium- dependent vasodilatory tone. Moreover, the amount of improvement with hormone supplementation and the additive effect of exercise will differ among HRT regimens. A 2-phase placebo controlled intervention trial employing state-of- the-art measurements of autonomic (e.g. micro neurography) and cardiovascular (e.g., high-resolution ultrasonography) function will be conducted. The expected results should provide new physiological and clinical information concerning the use of various HRT regimens and exercise for the primary prevention of reduced central arterial compliance with age and estrogen deficiency, the corresponding autonomic and cardiovascular functional benefits, as well as insight into the underlying mechanisms involved.