Aging, Sex, and Neural Cardiovascular Control During Dynamic Exercise

动态运动期间的衰老、性别和神经心血管控制

• 批准号: 7905184
• 负责人: PAUL J FADEL
• 金额: $ 37.38万
• 依托单位: UNIVERSITY OF MISSOURI-COLUMBIA
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-08-01 至 2013-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7905184
• 关键词: Acute myocardial infarction; Address; Adrenergic Agonists; Age; Age-Years; Aging; Arrhythmia; Automobile Driving; Baroreflex; Blood Circulation; Blood Pressure; Blood Vessels; Blood flow; Buffers; Cardiac; Cardiovascular system; Clinical; Cross-Sectional Studies; Data; Development; Doppler Ultrasound; Elderly; Estrogens; Event; Exercise; Exertion; Exhibits; Heart Arrest; Hormones; Human; Impairment; Individual; Intervention; Ischemia; Lead; Leg; Measures; Mediating; Menopause; Menstrual cycle; Metabolic; Mind; Muscle; Neck; Nerve; Ovarian hormone; Perfusion; Peripheral; Phase; Physical activity; Placebos; Postmenopause; Premenopause; Progesterone; Protocols documentation; Randomized; Reporting; Research Design; Rest; Risk; Skeletal Muscle; Stroke; Suction; Testing; Therapeutic; Tissues; Unsafe Sex; Vasomotor; Woman; Women' s Health; Work; age effect; age related; arm; blood pressure regulation; design; healthy aging; hemodynamics; improved; median nerve; meetings; men; neuromechanism; novel therapeutic intervention; older men; older women; placebo controlled study; pressure; protective effect; relating to nervous system; response; sex; vasoconstriction

DESCRIPTION (provided by applicant): Older individuals are increasingly being encouraged to exercise to maintain their physical well being and independence. However, studies have demonstrated that older subjects, particularly estrogen deficient postmenopausal women, have more pronounced increases in blood pressure (BP) during dynamic exercise. This exaggerated rise in BP during exercise is potentially dangerous because it can increase the occurrence of stroke and adverse cardiac events such as acute myocardial infarction, arrhythmia or cardiac arrest elevating the risk of performing physical activity as well as daily chores. To develop effective countermeasures to offset these potentially deleterious consequences, it is critical to identify the mechanism(s) driving the excessive rise in BP during physical exertion in the elderly. Given the importance of the arterial baroreflex (ABR) to neural cardiovascular control and responsiveness during exercise, a potential mechanism is impaired ABR function. Because postmenopausal women demonstrate the greatest elevation in BP during dynamic exercise and therefore, are at the highest risk, sex and ovarian hormone related differences will be examined. Aim 1 will determine whether an impaired ability of the ABR to buffer exercise-induced sympathoexcitation contributes to the greater BP response to dynamic exercise in older men and women. Furthermore, since augmented sympathetically-mediated vasoconstriction would not only cause an elevation in BP but may also limit blood flow to active muscle, aim 2 is designed to examine whether impairments in sympathetic vascular transduction contribute to a lower exercising muscle blood flow in older subjects during dynamic exercise. Finally, because decreases in ovarian hormones following menopause may alter neural cardiovascular and hemodynamic responses to exercise, aim 3 will consider how endogenous estrogen and progesterone concentrations alter ABR function and sympathetic control of the circulation during dynamic exercise in older and younger women. This important aspect of aging in women has been understudied in human studies of age-related alterations in cardiovascular responsiveness during exercise. These aims will be accomplished by assessing carotid baroreflex function (variable pressure neck chamber) at rest and during dynamic leg exercise while directly measuring sympathetic nerve activity (microneurography), BP, and leg blood flow (Doppler ultrasound) in young (20-30 yr) and older (60-75 yr) men and women. The findings from the proposed work may lead to the development of novel therapeutic interventions targeted at improving cardiovascular and hemodynamic responses during physical activity in the elderly. Indeed, if as preliminary data suggest, impairments in the ABR are identified as the underlying mechanism for the exaggerated pressor response to dynamic exercise in older subjects we will then be able to pursue interventions that could improve baroreflex function and potentially offset the deleterious neural cardiovascular responsiveness that manifests with aging. In addition, identifying how alterations in ovarian hormones influence neural cardiovascular control and responsiveness has important clinical therapeutic implications for women's health and the selection and usage of hormone replacement. PUBLIC RELEVANCE: Within 25 years the number of US citizens over 65 years of age is expected to reach 70 million. To maintain their physical well being and independence, older individuals are increasingly being encouraged to exercise. However, studies have demonstrated that older subjects, particularly estrogen deficient postmenopausal women, have more pronounced increases in blood pressure (BP) during dynamic exercise. This exaggerated rise in BP during exercise is potentially dangerous because it can increase the occurrence of stroke and adverse cardiac events such as acute myocardial infarction, arrhythmia or cardiac arrest elevating the risk of performing physical activity as well as daily chores. To develop effective countermeasures to offset these potentially deleterious consequences, it is important to identify the mechanism(s) driving the excessive rise in BP during physical exertion in the elderly. Given the importance of the arterial baroreflex to neural cardiovascular control and responsiveness during exercise, the studies outlined in this proposal are designed to investigate whether an impaired ability of the arterial baroreflex to buffer exercise-induced sympathoexcitation contributes to the greater BP response to dynamic exercise in older subjects. Because estrogen deficient postmenopausal women demonstrate the greatest elevation in BP during dynamic exercise and therefore, are at the highest risk, sex and ovarian hormone related differences will be examined.

描述（由申请人提供）：越来越多地鼓励老年人锻炼身体以保持身体健康和独立性。然而，研究表明，在动态运动过程中，老年受试者，尤其是绝经后女性缺乏雌激素，血压（BP）的升高更加明显。运动过程中BP的这种夸张的上升可能是危险的，因为它可以增加中风和心脏不良事件的发生，例如急性心肌梗塞，心律不齐或心脏骤停，从而升高了进行体育活动以及每日杂务的风险。为了开发有效的对策来抵消这些潜在的有害后果，至关重要的是，确定在老年人体力劳动期间推动BP过度上升的机制至关重要。鉴于动脉压力反射（ABR）对运动过程中神经心血管控制和反应的重要性，因此潜在的机制受损ABR功能。由于绝经后妇女在动态运动过程中表现出BP的升高最大，因此，将检查性和卵巢激素相关的差异。 AIM 1将确定ABR对缓冲运动引起的交感神经的能力是否有助于对老年男性和女性动态运动的更大反应。此外，由于增强的交感神经介导的血管收缩不仅会导致BP升高，而且还可能限制血液流向活性肌肉，AIM 2旨在检查交感神经血管转导的损害是否有助于在动态运动过程中降低较低的肌肉血液流动。最后，由于更年期后卵巢激素的降低可能会改变对运动的神经心血管和血液动力学反应，因此AIM 3将考虑内源性雌激素和孕激素浓度如何改变ABR功能和对年龄较小女性动态运动过程中循环的ABR功能和交感神经控制。在运动过程中与年龄相关的心血管反应性变化的人类研究中，女性衰老的这一重要方面已被研究。这些目标将通过在静止和动态腿运动过程中评估颈动脉降压功能（可变压颈室）来实现，同时直接测量年轻（20-30 yr）和年龄较大（60-75岁）男性和女性和女性和女性和女性和女性和女性和女性和女性和女性和女性和女性和女性和女性和女性和女性和女性和女性和女性和女性和女性和女性和女性和女性和女性和女性和女性和女性和女性和女性和女性和女性和女性和女性和女性和女性和女性和女性和女性和女性和女性和女性和女性和女性和女性和女性和女性和女性和女性和女性和女性和女性和女性和女性和女性和女性和女性和女性和女性和女性和女性。拟议工作的发现可能导致新的治疗干预措施的发展，该干预措施旨在改善老年人体育活动期间的心血管和血液动力学反应。确实，如果正如初步数据所暗示的那样，ABR中的损伤被确定为夸张的训练对较旧受试者动态运动反应的潜在机制，那么我们将能够采取能够提高巴罗雷弗Lex功能的干预措施，并可能抵消有害的神经心血管响应，而这些神经性心血管反应能够表现出与老化相处的表现。此外，确定卵巢激素的改变如何影响神经心血管控制和反应性具有重要的临床治疗意义，对女性的健康以及替代激素的选择和使用。公众相关性：在25年内，美国65岁以上的美国公民人数预计将达到7,000万。为了维持自己的身体健康和独立性，越来越多地鼓励老年人运动。然而，研究表明，在动态运动过程中，老年受试者，尤其是绝经后女性缺乏雌激素，血压（BP）的升高更加明显。运动过程中BP的这种夸张的上升可能是危险的，因为它可以增加中风和心脏不良事件的发生，例如急性心肌梗塞，心律不齐或心脏骤停，从而升高了进行体育活动以及每日杂务的风险。为了开发有效的对策以抵消这些潜在的有害后果，重要的是要确定在老年人体力劳动期间推动BP过度上升的机制。鉴于动脉压力反射在运动过程中对神经心血管控制和反应性的重要性，该提案中概述的研究旨在调查动脉压力反射对缓冲运动引起的交感神经激素的障碍能力是否有助于较大的受试者的BP对BP较大的BP反应。由于绝经后女性缺乏雌激素表现出动态运动过程中BP的升高最大，因此，将检查性别和卵巢激素相关的差异。