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Role of vascular hyperpolarization in muscle blood flow regulation in healthy humans

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dc.contributor.authorCrecelius, Anne Renee, author
dc.contributor.authorDinenno, Frank A., advisor
dc.contributor.authorChicco, Adam J., committee member
dc.contributor.authorTjalkens, Ronald B., committee member
dc.contributor.authorEarley, Scott, committee member
dc.date.accessioned2007-01-03T04:54:33Z
dc.date.available2014-06-30T04:54:32Z
dc.date.issued2013
dc.description.abstractThe following investigation composes a series of experiments with the overall aim of determining the role for vascular hyperpolarization via activation of inwardly-rectifying potassium (KIR) channels and Na+/K+-ATPase in the regulation of vascular tone in response to muscle contractions and ischaemia in young, healthy humans. We tested the general hypothesis that activation of KIR channels and Na+/K+-ATPase contributes in large part to the vasodilatory, hyperaemic, and sympatholytic responses observed in these conditions and this contribution is greater than that of other vasodilators, specifically nitric oxide (NO) and prostaglandins (PGs). The specific aims of each experiment were: 1) to determine whether K+-stimulated vascular hyperpolarization via activation of KIR channels and Na+/K+-ATPase mediates contraction-induced rapid vasodilatation in the human forearm; 2) to determine whether vascular hyperpolarization via activation of KIR channels and Na+/K+-ATPase contributes to the hyperaemic response at the onset of repeated muscle contractions, as well as to steady-state forearm blood flow during rhythmic handgrip exercise; 3) to determine whether vascular hyperpolarization via activation of KIR channels and Na+/K+-ATPase contributes to the observed blunting of sympathetically-mediated vasoconstriction that occurs during moderate intensity rhythmic forearm exercise; and 4) to determine whether vascular hyperpolarization via activation of KIR channels and Na+/K+-ATPase contributes to the observed reactive hyperaemia that occurs in the human forearm following release of temporary ischaemia. Our collective findings demonstrate a significant contribution of KIR channels and Na+/K+-ATPase activation to rapid vasodilatation following a single muscle contraction, the onset of exercise hyperaemia in response to repeated muscle contractions, steady-state muscle blood flow during rhythmic handgrip exercise and reactive hyperaemia following temporary ischaemia. In contrast to our hypothesis, we did not observe a significant contribution of KIR channels and Na+/K+-ATPase to the observed blunting of sympathetic α-adrenergic vasoconstriction that occurs during handgrip exercise. In all studies, any role of NO and PGs was modest, if present at all. Taken together, our findings indicate that during a variety of vasodilatory stimuli, there is a large contribution of pathways that are independent of NO and PGs, specifically activation of KIR channels and Na+/K+-ATPase. Hyperpolarization via activation of KIR channels and Na+/K+-ATPase represents a novel mechanistic pathway in the understanding of in vivo regulation of muscle blood flow in response to contractions and ischaemia. These findings may provide insight into understanding impaired vascular function in patient populations and as such, could represent a novel therapeutic target for reversing microvascular dysfunction.
dc.format.mediumborn digital
dc.format.mediumdoctoral dissertations
dc.identifierCrecelius_colostate_0053A_11680.pdf
dc.identifier.urihttp://hdl.handle.net/10217/78841
dc.languageEnglish
dc.language.isoeng
dc.publisherColorado State University. Libraries
dc.relation.ispartof2000-2019
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.subjectblood flow
dc.subjectvasoconstriction
dc.subjectpotassium
dc.subjecthyperpolarization
dc.subjecthumans
dc.subjectvasodilation
dc.titleRole of vascular hyperpolarization in muscle blood flow regulation in healthy humans
dc.typeText
dcterms.embargo.expires2014-06-30
dcterms.embargo.terms2014-06-30
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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