UBC Theses and Dissertations
Cerebrovascular and peripheral vascular regulation : role of oxidative stress Hansen, Alexander Bradley
Oxidative stress is ultimately determined by the balance between pro- (e.g. free radicals) and antioxidants (e.g. vitamin C). The purpose of this thesis was to examine the role and effect of a combined mixture of oral antioxidants (vitamin C, E, and alpha-lipoic acid) on peripheral and cerebrovascular regulation at both sea-level (344m; n = 11 participants) and at high altitude (5050m; n=10) where oxidative stress is markedly elevated. In a randomized and double-blinded design, flow-mediated dilation, cardiorespiratory, cerebral blood flow, and CO₂ and hypoxic cerebrovascular reactivity tests were conducted before and 90 mins following antioxidants (vitamin C, E, and alpha-lipoic acid) or a placebo control, previous work has shown antioxidant levels increased in blood plasma after 90 mins of ingestion. Following 10-12 days at 5050m, in a similar design, flow-mediated dilation, cardiorespiratory, and resting cerebral blood flow tests were obtained. The primary findings were: 1) antioxidants did not alter flow-mediated dilation, resting cerebral blood flow, cerebrovascular reactivity to CO₂ or hypoxia at sea-level; 2) similarly, at high-altitude (Nepal, 5050m), antioxidants did not alter flow-mediated dilation or resting cerebral blood flow. In conclusion, this study highlights that at both sea-level and high-altitude, acute oral administration of antioxidants does not alter FMD or cerebrovascular reactivity to CO₂ or hypoxia. Nevertheless, continued exploration of this methodology is recommended, especially in the form of more chronic dosing of antioxidants in various pathologies (e.g., chronic pulmonary obstructed disease, diabetes, coronary artery disease) who present with excessive oxidative stress and reductions in both antioxidant capacity and vascular function. This study received ethical approval from the University of British Columbia Clinical Research Ethics Board (ID: H16-00101). This research was supported by a NSERC Discovery grant and Canadian Research Chair in Cerebrovascular Physiology.
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