HRT and Exercise Effects on Central Arterial Compliance

描述(申请人提供)：候选人。候选人克里·L·克里。 莫罗博士是一名生理学家，目前由个人NRSA支持 来自国家航空安全局的。莫罗博士过去和现在的研究重点一直是物理 运动、衰老和心血管健康，尤其是女性。她 眼下的目标是获得新的研究和专业技能来帮助她 实现她培养一个成功的独立人士的长期目标 医疗外资助的老龄化研究项目。建议的KO1发展计划 计划应该为莫罗博士提供必要的培训，以实现她的目标 进球。 职业发展计划。莫罗博士的研究职业发展培训 活动包括：1)获得与以下方面相关的新研究技能 补充(例如，微阵列表达分析)建议的 研究计划；以及2)包括正式课程工作在内的结构化活动； 出席期刊俱乐部、系列研讨会和科学研讨会并发表演讲 会议；以及与她的指导团队的定期互动。 环境莫罗博士的培训环境应该很好。 赞助商和共同赞助商道格拉斯·西尔斯博士和温迪·科尔特是很好的- 著名的外部资助的科学家，有成功的良好记录 生物医学老化研究方面的指导。他们受到了几个人的称赞 将在培训的特定领域提供指导的咨询导师 计划。其他从事老龄化研究的教师则加强了环境保护。 研究。总体目标是确定3种药物的相对疗效。 常用激素替代疗法(HRT)，定期有氧 运动，以及激素替代疗法和运动相结合改善中枢 (颈动脉)顺应性、相关的功能优势和 绝经后健康久坐不动的雌激素缺乏的潜在机制 女人。一般的假设是，HRT和运动将独立和 此外，改善动脉顺应性，这将反过来导致 功能益处(例如，心脏迷走神经压力感受性反射敏感性的改善 和左心室功能/结构)，而这些有利的适应 将部分地通过交感神经张力的减少(仅限HRT)和/或 减少氧化应激相关的血管内皮细胞改善- 依从性血管扩张张力。此外，激素的改善量 补充和运动的相加效应在不同的激素替代疗法中会有所不同 养生法。一项两阶段的安慰剂对照干预试验 自主神经(如显微神经学)和心血管的最新测量 (例如，高分辨率超声)功能将被执行。这个 预期结果应提供新的生理和临床信息 关于各种HRT方案的使用和小学生的锻炼 预防随年龄和雌激素而降低的中央动脉顺应性 缺乏，相应的自主神经和心血管功能 好处，以及对所涉及的基本机制的洞察。

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.