Role of the sympatho-adrenal system in the regulation of peripheral vascular tone in healthy aging humans

Abstract

The following dissertation is comprised of a series of experiments with the overall aim of determining the role of the sympatho-adrenal system in the regulation of peripheral vascular tone in normal, healthy aging humans. Aging is associated with a reduction in aerobic capacity and elevated risk of cardiovascular disease. The decline in aerobic capacity could be a consequence of impaired O2 delivery, directly attributed to attenuated skeletal muscle blood flow. Attenuated skeletal muscle blood flow reflects a decline in the ability to adequately regulate peripheral vascular tone, either due to elevated vasoconstrictor signaling or decreased vasodilator signaling. Understanding the regulation of peripheral vascular tone and what leads to its decline with age could lend itself to the creation of treatments capable of improving oxygen (O2) delivery by increasing muscle blood flow. Net vascular tone is determined by the balance between vasodilator and vasoconstrictor tone within the vessel. With age, there is both a decrease in the production of local endothelium-dependent dilators as well as an increase in resting sympathetic nervous system (SNS) activity, which can lead to elevations in vasoconstrictor tone, potentially limiting blood flow to skeletal muscle. To better understand the role of the SNS in regulation of peripheral vascular tone with age, we can use established pharmacology and locally inhibit the sympatho-adrenal system and observe the net blood flow response during conditions that challenge the vascular system such as lowered O2 delivery (systemic hypoxia) and elevated peripheral O2 demand (exercise) in both young and older adults. We hypothesize that older adults will exhibit impaired regulation of peripheral vascular tone to both graded systemic hypoxia and graded handgrip exercise. Further, we hypothesize that the age-associated impairment is attributed to elevated vasoconstrictor tone mediated from the SNS. The primary findings of this dissertation are that older adults exhibit impaired regulation of peripheral vascular tone in response to physiological stressors (systemic hypoxia and handgrip exercise). Contrary to our hypothesis, the age-associated impairment was not directly attributed to elevated vasoconstrictor tone from the SNS and is likely due to attenuated vasodilatory signaling in older adults.