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 Health 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.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL093167-05
Application #
8319257
Study Section
Clinical and Integrative Cardiovascular Sciences Study Section (CICS)
Program Officer
Nelson, Cheryl R
Project Start
2008-08-01
Project End
2013-07-31
Budget Start
2012-08-01
Budget End
2013-07-31
Support Year
5
Fiscal Year
2012
Total Cost
$370,013
Indirect Cost
$122,513
Name
University of Missouri-Columbia
Department
Pharmacology
Type
Schools of Medicine
DUNS #
153890272
City
Columbia
State
MO
Country
United States
Zip Code
65211
Reynolds, Leryn J; Credeur, Daniel P; Holwerda, Seth W et al. (2015) Acute inactivity impairs glycemic control but not blood flow to glucose ingestion. Med Sci Sports Exerc 47:1087-94
Padilla, Jaume; Jenkins, Nathan T; Laughlin, M Harold et al. (2014) Blood pressure regulation VIII: resistance vessel tone and implications for a pro-atherogenic conduit artery endothelial cell phenotype. Eur J Appl Physiol 114:531-44
Credeur, Daniel P; Holwerda, Seth W; Boyle, Leryn J et al. (2014) Effect of aging on carotid baroreflex control of blood pressure and leg vascular conductance in women. Am J Physiol Heart Circ Physiol 306:H1417-25
Horiuchi, Masahiro; Fadel, Paul J; Ogoh, Shigehiko (2014) Differential effect of sympathetic activation on tissue oxygenation in gastrocnemius and soleus muscles during exercise in humans. Exp Physiol 99:348-58
Jenkins, Nathan T; Padilla, Jaume; Boyle, Leryn J et al. (2013) Disturbed blood flow acutely induces activation and apoptosis of the human vascular endothelium. Hypertension 61:615-21
Fairfax, Seth T; Holwerda, Seth W; Credeur, Daniel P et al. (2013) The role of ýý-adrenergic receptors in mediating beat-by-beat sympathetic vascular transduction in the forearm of resting man. J Physiol 591:3637-49
Fairfax, Seth T; Padilla, Jaume; Vianna, Lauro C et al. (2013) Spontaneous bursts of muscle sympathetic nerve activity decrease leg vascular conductance in resting humans. Am J Physiol Heart Circ Physiol 304:H759-66
Greaney, Jody L; Schwartz, Christopher E; Edwards, David G et al. (2013) The neural interaction between the arterial baroreflex and muscle metaboreflex is preserved in older men. Exp Physiol 98:1422-31
Boyle, Leryn J; Credeur, Daniel P; Jenkins, Nathan T et al. (2013) Impact of reduced daily physical activity on conduit artery flow-mediated dilation and circulating endothelial microparticles. J Appl Physiol (1985) 115:1519-25
Deo, Shekhar H; Jenkins, Nathan T; Padilla, Jaume et al. (2013) Norepinephrine increases NADPH oxidase-derived superoxide in human peripheral blood mononuclear cells via *-adrenergic receptors. Am J Physiol Regul Integr Comp Physiol 305:R1124-32

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