Aging, Sex, and Neural Cardiovascular Control During Dynamic Exercise

描述（由申请人提供）：越来越多的老年人被鼓励锻炼身体，以保持身体健康和独立。然而，研究表明，年龄较大的受试者，特别是雌激素缺乏的绝经后妇女，在进行动态运动时血压（BP）升高更为明显。运动时血压的过度升高是潜在的危险，因为它会增加中风和急性心肌梗死、心律失常或心脏骤停等不良心脏事件的发生，增加进行体育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，确定导致老年人体力消耗时血压过度升高的机制至关重要。鉴于运动中动脉压力反射（ABR）对神经心血管控制和反应性的重要性，ABR功能受损可能是其潜在机制。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的差异。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产生更大的血压反应。此外，由于交感神经介导的血管收缩增强不仅会导致血压升高，还可能限制活跃肌肉的血流量，目的2旨在研究交感血管转导损伤是否会导致老年人在动态运动中运动肌肉血流量降低。最后，由于绝经后卵巢激素的降低可能会改变神经心血管和血液动力学对运动的反应，目的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在动态运动期间ABR功能和交感神经循环控制。女性衰老的这一重要方面在运动中心血管反应性年龄相关改变的人类研究中尚未得到充分研究。这些目标将通过评估静止和动态腿部运动时的颈动脉压力反射功能（变压颈室），同时直接测量年轻（20-30岁）和老年（60-75岁）男性和女性的交感神经活动（微神经造影）、血压和腿部血流（多普勒超声）来实现。这项工作的发现可能会导致新的治疗干预措施的发展，这些干预措施旨在改善老年人身体活动期间的心血管和血液动力学反应。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压力反应的潜在机制，那么我们将能够采取干预措施，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的神经心血管反应。此外，确定卵巢激素的变化如何影响神经心血管控制和反应性，对妇女健康和激素替代的选择和使用具有重要的临床治疗意义。公共相关性：在25年内，65岁以上的美国公民数量预计将达到7000万。为了保持身体健康和独立，越来越多的老年人被鼓励锻炼。然而，研究表明，年龄较大的受试者，特别是雌激素缺乏的绝经后妇女，在进行动态运动时血压（BP）升高更为明显。运动时血压的过度升高是潜在的危险，因为它会增加中风和急性心肌梗死、心律失常或心脏骤停等不良心脏事件的发生，增加进行体育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，确定导致老年人体力消耗时血压过度升高的机制非常重要。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，本提案中概述的研究旨在研究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导致老年受试者对动态运动产生更大的血压反应。由于雌激素缺乏的绝经后妇女在动态运动时血压升高幅度最大，因此风险最高，因此将检查性别和卵巢激素相关的差异。

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.