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: 7845766
• 负责人: PAUL J FADEL
• 金额: $ 16.33万
• 依托单位: UNIVERSITY OF MISSOURI-COLUMBIA
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-07-01 至 2012-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7845766
• 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; Classification; 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; Upper arm; Vasomotor; Woman; Women' s Health; Work; age effect; age related; 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）：老年人越来越多地被鼓励锻炼，以保持身体健康和独立性。然而，研究表明，老年受试者，特别是雌激素缺乏的绝经后妇女，在动态运动期间血压（BP）有更明显的增加。运动期间血压的这种过度升高具有潜在的危险性，因为它会增加中风和不良心脏事件（如急性心肌梗死、心律失常或心脏骤停）的发生率，从而增加进行体力活动和日常家务的风险。为了制定有效的对策来抵消这些潜在的有害后果，确定老年人体力消耗期间血压过度升高的机制至关重要。鉴于动脉压力反射（ABR）的重要性，在运动过程中的神经心血管控制和反应性，一个潜在的机制是受损的ABR功能。由于绝经后妇女在动态运动中血压升高最大，因此风险最高，因此将检查性别和卵巢激素相关差异。目的1将确定ABR缓冲运动诱导的交感神经兴奋的能力受损是否有助于老年男性和女性对动态运动的更大BP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血压升高，而且还可能限制血流到活动肌肉，目的2旨在检查交感神经血管转导的损伤是否有助于老年受试者在动态运动期间较低的运动肌肉血流量。最后，由于绝经后卵巢激素的减少可能会改变运动对神经心血管和血液动力学的反应，目标3将考虑内源性雌激素和孕激素浓度如何改变老年和年轻女性动态运动过程中ABR功能和交感神经对循环的控制。女性衰老的这一重要方面在运动期间与年龄相关的心血管反应性变化的人类研究中得到了充分的研究。这些目标将通过评估年轻（20-30岁）和老年（60-75岁）男性和女性在静息和动态腿部运动期间的颈动脉压力感受器反射功能（可变压力颈室），同时直接测量交感神经活动（显微神经造影术）、BP和腿部血流（多普勒超声）来实现。这项研究的结果可能会导致开发新的治疗干预措施，旨在改善老年人体力活动期间的心血管和血流动力学反应。事实上，如果如初步数据所示，ABR的损伤被确定为老年受试者对动态运动的过度升压反应的潜在机制，那么我们将能够寻求可以改善压力反射功能并潜在地抵消随着年龄增长而表现出的有害神经心血管反应的干预措施。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，对妇女的健康和激素替代的选择和使用具有重要的临床治疗意义。公众相关性：在25年内，65岁以上的美国公民人数预计将达到7000万。为了保持他们的身体健康和独立性，老年人越来越多地被鼓励锻炼。然而，研究表明，老年受试者，特别是雌激素缺乏的绝经后妇女，在动态运动期间血压（BP）有更明显的增加。运动期间血压的这种过度升高具有潜在的危险性，因为它会增加中风和不良心脏事件（如急性心肌梗死、心律失常或心脏骤停）的发生率，从而增加进行体力活动和日常家务的风险。为了制定有效的对策来抵消这些潜在的有害后果，重要的是要确定驱动老年人体力消耗期间血压过度升高的机制。考虑到动脉压力反射对运动期间神经心血管控制和反应的重要性，本提案中概述的研究旨在调查动脉压力反射缓冲运动诱导的交感神经兴奋的能力受损是否有助于老年受试者对动态运动的更大BP反应。由于雌激素缺乏的绝经后妇女在动态运动中血压升高最大，因此风险最高，因此将检查性别和卵巢激素相关的差异。