UBC Theses and Dissertations
The impact of high altitude on endothelial function in humans Tymko, Michael Martin
Previous work has demonstrated that ascent to high altitude results in endothelial impairment (i.e. reduced); however, the mechanism(s) governing this impairment remain unclear. The overall objective of the current thesis, addressed in three separate studies, was to determine the role of the sympathetic nervous system (SNS) on endothelial function after ascent to high altitude. Study #1 investigated the effects of exercise-induced elevations in sympathetic nervous activity (SNA) on endothelial function [via non-invasive flow-mediated dilation (FMD)] at sea level (344m) and high altitude (3800m). The findings from this study demonstrated that endothelial function was not reduced at high altitude compared to sea level at rest. Furthermore, at sea-level, endothelial function was reduced via SNS related pathways after moderate intensity exercise; however, this was not observed at high altitude. Study #2 examined the influence of transient manipulations of SNA [via lower-body differential pressure] on endothelial function (via FMD) at sea level (344m) and high altitude (5050m). The primary findings indicated that endothelial function was impaired at rest, and at both sea level and high altitude, endothelial function was not altered after manipulating SNA. Based on previous investigations and studies #1 and #2 of the current thesis, we hypothesized that endothelial function was only reduced at altitudes >4000m. Study #3 assessed vascular function (via intra-arterial infusion of acetylcholine and sodium nitroprusside) at rest before and after local forearm autonomic blockade at sea level (344m) and high altitude (4300m) in lowlanders and Andean highlanders with and without excessive erythrocytosis (EE). The primary findings were that endothelial function was reduced in lowlanders at high altitude, and this reduction was abolished after local autonomic blockade. In addition, Andean participants with EE had reduced endothelial function compared to healthy Andean highlanders, which was partially normalized after local autonomic blockade. Collectively, the findings from study #3 demonstrate that high altitude related reductions in endothelial function are governed by elevated SNA. The observed disparity on the impact of high altitude on endothelial function at rest is likely related to the severity, and potentially the length of altitude exposure. In summary, we observed that endothelial function is reduced at rest at altitudes >4000m (e.g. study #2 and #3), and provide data indicating that manipulating SNA at high altitude via exercise and lower-body differential pressure has no impact on endothelial function (e.g. study #1 and #2), but endothelial function is fully restored in lowlanders, and partially restored in Andean highlanders with EE, after administration of full autonomic blockade (e.g. study #3).
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