2026-09-22T13:22:14Zhttps://api.mountainscholar.org/server/oai/request

oai:mountainscholar.org:10217/1703732025-12-30T03:25:50Zcom_10217_100532com_10217_100000com_10217_100360com_10217_100303col_10217_100538col_10217_100361

Chaplin, Nathan L., author Amberg, Gregory, advisor DeLuca, Jennifer, committee member Tamkun, Michael, committee member Tsunoda, Susan, committee member 2016-01-11T15:13:54Z 2016-01-11T15:13:54Z 2015 Chaplin_colostate_0053A_13348.pdf http://hdl.handle.net/10217/170373 https://doi.org/10.25675/3.018612 Resistance arteries are a major point of physiological regulation of blood flow. Increases in vessel wall stress or sympathetic activity stimulate vascular wall angiotensin signaling, resulting in smooth muscle contraction which directly increases peripheral resistance. Calcium influx through voltage-gated L-type calcium channels underlies vascular smooth muscle contraction. Roughly half of calcium influx in these cells occurs through a small number of persistently active channels, whose activity increases with membrane depolarization. The number of channels gating in this manner is increased by activation of angiotensin receptors on the cell membrane, and basal L-type channel activity is increased during hypertension. Reactive oxygen species are also generated by vascular smooth muscle in response to vessel stretch and by several paracrine signaling pathways including angiotensin signaling. Oxidative stress and augmented calcium handling resulting from chronic angiotensin signaling in the vasculature each contribute to enhanced vessel reactivity, pathological inflammation and vessel remodeling associated with hypertension. This study uses a multidisciplinary approach to investigate the role of hydrogen peroxide in angiotensin signaling in vascular smooth muscle. Using calcium- and redox-sensitive fluorescent indicators, local generation of hydrogen peroxide by NAD(P)H oxidase and mitochondria are shown to synergistically promote PKC-dependent persistent gating of plasma membrane L- type calcium channels in response to angiotensin II. We show that broad inhibition of hydrogen peroxide signaling by catalase and targeted inhibition of mitochondrial reactive oxygen species production attenuates cerebral resistance artery constriction to angiotensin. We further demonstrate the role of endothelium-independent mitochondrial reactive oxygen species in development of enhanced vessel tone and smooth muscle calcium in a murine model of hypertension. Together, these findings contribute to the understanding of intracellular calcium and oxidative signaling in vascular physiology and disease and may provide insight into local signaling dynamics involving these second messengers in various other systems. born digital doctoral dissertations English eng Colorado State University. Libraries 2000-2019 Copyright 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. angiotensin L-type calcium channel mitochondria NAD(P)H oxidase reactive oxygen species vascular smooth muscle Oxidant-dependent regulation of L-type calcium channel activity by angiotensin in vascular smooth muscle Text Doctor of Philosophy (Ph.D.) Doctoral Biomedical Sciences Colorado State University This 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). open.access