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On the role of circulating ATP in vascular control at rest and during exercise of aging humans




Kirby, Brett Sean, author
Dinenno, Frank A., advisor
Earley, Scott, 1963-, committee member
Chicco, Adam J., committee member
Gotshall, Robert William, 1945-, committee member

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The following investigation composes a series of experiments with the overall aim of determining the role for the circulating nucleotide adenosine triphosphate (ATP) in vascular control at rest and during exercise in humans of advanced age. We tested the general hypothesis that ATP has definite vasodilator and sympatholytic vasomotor properties in young adults during exercise, but that these actions are impaired in older adults; and that endogenously circulating levels of ATP are diminished during exercise in the aged population. Specifically, the experiments are outlined as such: 1) to determine whether exogenous ATP can modulate α-adrenergic vasoconstriction in the human forearm of young adults, 2) to determine whether vasodilator responsiveness to exogenous ATP is impaired in aging humans, and the contribution of adenosine to ATP-mediated vasodilation in aging humans, 3) to determine whether the ability of exogenous ATP to modulate α-adrenergic vasoconstriction in the human forearm of older adults is impaired similar to the typical response observed during exercise in aged humans, 4) to determine whether endogenous venous plasma [ATP] and ATP release is diminished during mild-to-moderate exercise in aging humans. Our collective findings indicate that alterations in the contribution of ATP to vascular tone in aging humans exist and may in part be a potential mechanism by which aged adults have reductions in oxygen delivery to active skeletal muscle. In particular, circulating exogenous ATP has the ability to significantly blunt α-adrenergic vasoconstriction in young adults similar to that observed during exercise. In contrast to our hypothesis, the vasodilatory responsiveness and sympatholytic properties of exogenous ATP remain intact in aging humans. However, older adults demonstrate reduced venous plasma [ATP] and impaired ATP release during graded mild-to-moderate handgrip exercise which is associated with attenuations in skeletal muscle vasodilation and blood flow. Taken together, it is our belief that the typically observed impairments in skeletal muscle vasodilation and the inability to offset sympathetic vasoconstrictor tone during exercise is in part due to diminished endogenous levels of circulating ATP in aging humans. On the whole, ATP appears to be a significant regulator of vascular control in humans, and may act as a potential mechanism which in part explains the typically observed reductions in skeletal muscle blood flow and oxygen delivery to active tissue in aged humans thereby predisposing this population to an elevated risk for cardiovascular diseases, age-related declines in exercise capacity/tolerance, and an overall decline in quality of life in this population.


Department Head: Richard Gay Israel.

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