Doctor of Philosophy
Shoemaker, Kevin J.
The overall objective of this dissertation was to determine the impact of age, sex, and sex hormones on the discharge behaviours of muscle sympathetic action potentials (APs) as well as the corresponding changes in peripheral vasoconstriction and blood pressure at rest and during exercise. The microneurographic technique was employed to record multi-unit muscle sympathetic nerve activity (MSNA), with a continuous wavelet transform applied post-hoc to evaluate APs within the recorded neurogram. Study One examined the impact of aging on the central and peripheral arcs of the sympathetic baroreflex under resting conditions. This study revealed that middle-aged-to-older adults demonstrated heightened sympathetic baroreflex control of MSNA and AP discharge (i.e., greater central arc), but attenuated sympathetic transduction into blood pressure (i.e., attenuated peripheral arc). Therefore, it appears that the interactive nature between the central and peripheral baroreflex arcs are preserved with human aging, and that greater baroreflex control of sympathetic discharge may be compensatory for attenuated sympathetic transduction amongst older adults. Study Two investigated the interactive effects of age and sex on sympathetic vascular transduction (i.e., the transmission of MSNA into peripheral vasoconstriction) as well as the central and peripheral arcs of the baroreflex at rest. We observed that age, but not sex, affected sympathetic vascular transduction, with older adults (regardless of sex) demonstrating attenuated vasoconstrictor responses following bursts of sympathetic discharge. Additionally, we found that males, but not females (regardless of age) demonstrated a relationship between the central and peripheral baroreflex arcs, indicating that females do not rely on this compensatory neuro-cardiovascular relationship to regulate arterial blood pressure at rest. Study Three assessed the interactive effects of age and sex on the neuro-cardiovascular responses to fatiguing exercise. During rhythmic handgrip exercise, we found that older males demonstrated the largest increases in blood pressure and peripheral resistance compared to young adults and older females, despite having the smallest increases in efferent sympathetic nerve traffic. Notably, amongst males, testosterone was inversely related with the change in blood pressure, but positively related with AP recruitment, indicating that the lower testosterone levels may be driving these larger pressor and attenuated sympathetic responses amongst older males. Conversely, the loss of estradiol following menopause did not affect the neuro-cardiovascular responses to fatiguing rhythmic handgrip exercise amongst women. Finally, Study Four aimed to determine the role of biological sex and oral contraception on sympathetic AP discharge as well as the vasoconstrictor responses to changes in AP discharge during fatiguing static handgrip exercise amongst young adults. Here, we found that males had larger increases in AP discharge than females (particularly naturally menstruating females) during static handgrip exercise; however, no differences were observed between females using oral contraceptive pills and naturally menstruating females. Conversely, both males and females using oral contraception demonstrated greater leg vasoconstriction during exercise compared to naturally menstruating females. Therefore, the transduction of sympathetic nerve traffic into vasoconstriction is attenuated in naturally menstruating females compared to males and females using oral contraception. Overall, this series of studies provides new knowledge regarding the impact of age, sex, as well as endogenous and exogenous sex hormones on the regulation of muscle sympathetic AP discharge and the peripheral vasomotor responses to these efferent vasoconstrictor signals.
Summary for Lay Audience
The sympathetic nervous system, which sends precise, goal-directed messages along nerves to communicate with various organs to ensure that blood pressure is maintained within an optimal range and that blood flow is distributed to vital organs like the brain and the heart. These messages are made up of electrical signals called action potentials. During periods of stress (like exercise), the sympathetic nervous system adjusts these messages toward the heart and the blood vessels by increasing the size, number, and timing of action potentials to permit controlled increases in blood pressure and blood flow, ensuring that sufficient oxygen is delivered throughout the body. Although the sympathetic nervous system plays an important role in human survival and performance, there is growing evidence that its control of the blood vessels in the body change across the lifespan and differ between males and females. This dissertation provides new insight into how factors like human aging, biological sex (i.e., males and females), and sex hormones (i.e., testosterone, estrogen, progesterone) affect the action potential messages used by the sympathetic nervous system to communicate with the blood vessels, and how these factors affect the responsiveness of blood vessels to the carefully crafted messages of the sympathetic nervous system.
D'Souza, Andrew W., "The sympathetic neural control of the circulation at rest and during exercise: effects of age, biological sex, and sex hormones" (2023). Electronic Thesis and Dissertation Repository. 9425.
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Available for download on Friday, December 01, 2023