Endothelial-dependent, shear-induced vasodilation is rate-sensitive.
Item
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Title
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Endothelial-dependent, shear-induced vasodilation is rate-sensitive.
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Identifier
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AAI9917635
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identifier
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9917635
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Creator
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Butler, Peter Jonathan.
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Contributor
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Co-Mentors: Sheldon Weinbaum | Daniel E. Lemons
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Date
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1999
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Language
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English
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Publisher
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City University of New York.
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Subject
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Engineering, Biomedical | Applied Mechanics | Biophysics, Medical
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Abstract
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In this dissertation, we begin by presenting a background on blood-flow regulation, shear sensitivity of the endothelium, and endothelial mechanics. We then demonstrate, for the first time in arterioles, the existence of an endothelial mechanism to sense shear-stress magnitude and shear-stress rate-of-change and we proceed to quantify the arterioles' response. Finally, we describe a novel experimental technique to measure the membrane fluidity of cells under shear; membrane fluidity is a cell parameter which is hypothesized to play a role in endothelial shear mechanotransduction.;To evaluate the relative roles of shear magnitude and rate of change of shear in endothelial mediated vascular dilation, we developed a novel feedback control system in which shear stress (T) and the temporal shear gradient (TSG) were prescribed and dynamically controlled in isolated rat cremaster 1A arterioles. This system was used to assess the roles of T and TSG in the initial, transient vasodilations and the secondary, sustained vasodilations in response to steps and ramps in shear stress. Results showed that there exist two fundamentally different vasodilatory responses to shear stress which are mediated by microvascular endothelium: one being potent, transient, and rate-sensitive and the other being more modest, sustained, and magnitude-sensitive.;Finally, we hypothesize that the cell membrane may be a shear sensitive organelle and that shear stress may alter cell membrane fluidity, a parameter known to modulate membrane protein function. We proceeded to develop a system in which cell membrane fluidity was measured on the confocal microscope using fluorescent recovery after photobleaching (FRAP) while the cells were sheared in a parallel plate flow chamber. Results show that this system can enable us to obtain fluidity measurements in as little as one second and will therefore be useful in measuring the time rate-of-change of membrane fluidity during various shear transients.
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Type
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dissertation
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Source
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PQT Legacy CUNY.xlsx
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degree
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Ph.D.
