Aging, Sex, and Neural Cardiovascular Control During Dynamic Exercise

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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.