Completing a 4,486 km Multi-stage Ultramarathon Increases Arterial Stiffness and Alters Circulating Factors That Cause Endothelial Cell Dysfunction
Authors: Udovich‘ CeAnn , Ludwig Katelyn , Craighead Daniel , Schütz Uwe , Schmidt-Trucksäss Arno , Seals Douglas 
Published: May 2024

Background: Guideline-based levels of aerobic exercise can improve vascular function, in part by decreasing arterial stiffness and oxidative stress, and increasing nitric oxide bioavailability. However, results from single-stage ultramarathons and ultra-endurance feats in modalities such as biking or triathlons suggest that excessive levels of aerobic exercise may impair vascular function. Some athletes will complete multi-day ultra-endurance events. One such example is the TransEurope FootRace (TEFR), a transcontinental ultramarathon in which participants cover 4,486 km in 64 days. However, the impact of this multi-stage ultramarathon on vascular function is unknown. Purpose: Here, we tested the hypotheses that completing the TEFR would increase arterial stiffness measured in vivo and alter circulating factors that increase reactive oxygen species (ROS) production and reduce the activation of endothelial nitric oxide synthase (eNOS) ex vivo. Methods: Data were obtained from 29 men and 1 woman (48±11 years of age) before and within 10 days of completing the TEFR. Arterial stiffness was assessed as carotid-femoral pulse wave velocity measured via MRI. Human aortic endothelial cells (HAECs) in culture were exposed to 10% subject plasma, then stained with florescent probes to detect basal ROS production (CellROX). Protein concentrations of phosphorylated(p)‐eNOS(S1177), a primary activation site of eNOS, were determined in the cultured HAECs via WES. Protein expression was normalized to total protein in the sample. P-eNOS relative to total protein was compared with total eNOS relative to total protein to determine activated eNOS. Results: Completing the TEFR caused a clinically significant 31% increase in carotid-femoral pulse wave velocity (pre-race: 610±37 cm/s, post-race: 800±99 cm/s; p=0.0374). ROS production increased by 40% in HAECs exposed to post-race plasma compared with pre-race plasma (pre-race: 1308±86 AU, post-race: 1836±131 AU; p<0.0001). P-eNOS(S1177) decreased by 71% in HAECs after compared with before the race (pre-race: 0.080±0.038 AU; post-race: 0.023±0.005 AU; p=0.0047), whereas total eNOS was unchanged (pre-race: 1.646±0.328 AU, post-race 1.634±0.6533 AU, p=0.9137), suggesting a marked decrease in eNOS activation after the race. Conclusions: These findings indicate that completing a 64-day, 4,486 km ultramarathon increases arterial stiffness and changes factors in the circulation that increase ROS production and decrease eNOS activation, denoting reduced endothelial cell functioning. Performing this level of prolonged, strenuous physical exercise impairs vascular function in healthy highly trained adults. K01HL153326; SCHU 2514/1-1; SCHU 2514/1-2. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.