Novel role of acetylcholine in vascular control in humans

Terwoord, Janée D., author
Dinenno, Frank A., advisor
Amberg, Gregory C., committee member
Chicco, Adam J., committee member
Gentile, Christopher L., committee member
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The vascular endothelium is remarkably sensitive to the molecule acetylcholine (ACh), which binds to muscarinic receptors to initiate endothelium-dependent vasodilation. Although vasodilatory responsiveness to ACh is considered the gold standard index of endothelial function, an obligatory role for ACh in peripheral blood flow control has been challenging to elucidate. Thus, muscarinic ACh receptors on endothelial cells are widely considered to be evolutionary remnants with no real physiological function in humans. Administration of exogenous ACh amplifies endothelial sensitivity to other vasodilatory stimuli and blunts sympathetic vasoconstrictor signaling; therefore, we sought to determine whether endogenous ACh contributes to these processes in vivo. Accordingly, the overall goal of this dissertation research was to evaluate the role of ACh in modulating sympathetic α adrenergic vasoconstriction and eliciting vasodilation in healthy, young adults. The primary findings are that 1) ACh interacts with the endothelium-dependent vasodilator adenosine triphosphate (ATP) to augment vasodilation and limit α1 adrenergic vasoconstriction in the skeletal muscle resistance vasculature, 2) endogenous ACh blunts sympathetic vasoconstriction within active skeletal muscle and is an obligatory mechanism of functional sympatholysis during exercise at high intensities, and 3) ACh mediates flow-induced vasodilation of conduit arteries in response to sustained and transient increases in shear rate induced by handgrip exercise and reactive hyperemia, respectively. Collectively, these studies reveal a novel, physiological role of ACh in peripheral blood flow regulation in humans.
Includes bibliographical references.
2020 Summer.
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flow-mediated dilation
functional sympatholysis
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