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Novel role of acetylcholine in vascular control in humans

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dc.contributor.authorTerwoord, Janée D., author
dc.contributor.authorDinenno, Frank A., advisor
dc.contributor.authorAmberg, Gregory C., committee member
dc.contributor.authorChicco, Adam J., committee member
dc.contributor.authorGentile, Christopher L., committee member
dc.date.accessioned2020-08-31T10:12:02Z
dc.date.available2021-08-24T10:12:02Z
dc.date.issued2020
dc.description.abstractThe 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.
dc.format.mediumborn digital
dc.format.mediumdoctoral dissertations
dc.identifierTerwoord_colostate_0053A_16189.pdf
dc.identifier.urihttps://hdl.handle.net/10217/211805
dc.languageEnglish
dc.language.isoeng
dc.publisherColorado State University. Libraries
dc.relation.ispartof2020-
dc.rightsCopyright and other restrictions may apply. User is responsible for compliance with all applicable laws. For information about copyright law, please see https://libguides.colostate.edu/copyright.
dc.subjectendothelium
dc.subjectflow-mediated dilation
dc.subjectvascular
dc.subjectexercise
dc.subjectacetylcholine
dc.subjectfunctional sympatholysis
dc.titleNovel role of acetylcholine in vascular control in humans
dc.typeText
dcterms.embargo.expires2021-08-24
dcterms.embargo.terms2021-08-24
dcterms.rights.dplaThis Item is protected by copyright and/or related rights (https://rightsstatements.org/vocab/InC/1.0/). You are free to use this Item in any way that is permitted by the copyright and related rights legislation that applies to your use. For other uses you need to obtain permission from the rights-holder(s).
thesis.degree.disciplineHealth and Exercise Science
thesis.degree.grantorColorado State University
thesis.degree.levelDoctoral
thesis.degree.nameDoctor of Philosophy (Ph.D.)

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