Endothelium-Dependent Vasodilation is Impaired in Chronic Spinal Cord Injury and is Associated with Oxidative Stress

Park, A. J.; DeSouza, C. A.; Madera, G.; Morey, C.; Summers, M.; Garcia, V. P.; Berry, A. R.; Ruzenne, S. T.; DeSouza, N.; Holzer, J. P.; Deitemeyer, A.; Greiner, J. J.; Stauffer, B. L.

doi:10.64898/2026.05.27.728335

bioRxiv · 10.64898/2026.05.27.728335

Endothelium-Dependent Vasodilation is Impaired in Chronic Spinal Cord Injury and is Associated with Oxidative Stress

Park, A. J.·DeSouza, C. A.·Madera, G.·Morey, C.·Summers, M.·Garcia, V. P.·Berry, A. R.·Ruzenne, S. T.·DeSouza, N.·Holzer, J. P.·Deitemeyer, A.·Greiner, J. J.·Stauffer, B. L.

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Abstract

BackgroundIndividuals with spinal cord injury (SCI) experience accelerated atherosclerotic cardiovascular disease that is not fully explained by traditional risk factors. Endothelial dysfunction is a key mechanism in atherosclerosis. We tested the hypothesis that endothelium-dependent vasodilation is impaired in adults with SCI and is due, at least in part, to oxidative stress. MethodsTwenty-four adults (age:19-58 yr) free of overt cardiometabolic disease were studied: 12 non-injured adults (9 M/3 F) and 12 adults with chronic SCI (8 M/4 F; time since injury 1.5 - 25 years). Forearm blood flow was determined (FBF; via strain-gauge plethysmography) in response to intra-arterial infusion of acetylcholine and isoproterenol in the absence and presence of the antioxidant vitamin C as well as the FBF response to sodium nitroprusside. ResultsAdults with SCI demonstrated significantly lower vasodilator response to acetylcholine (from 4.1{+/-}0.6 to 10.7{+/-}2.6 mL/100 mL tissue/min vs 4.1{+/-}1.1 to 15.7{+/-}3.4 mL/100 mL tissue/min) and isoproterenol (4.0{+/-}0.6 to 11.2{+/-}2.2 mL/100 mL tissue/min vs 4.3{+/-}1.0 to 15.0{+/-}2.6 mL/100 mL tissue/min) compared with non-injured adults. FBF response to sodium nitroprusside was not significantly different between the groups. Co-infusion of vitamin C significantly increased the vasodilator response to acetylcholine (~45%) and isoproterenol (~25%) in the adults with SCI to levels comparable with non-injured adults. ConclusionsChronic SCI is associated with endothelial-dependent vasodilator dysfunction. Impaired vasodilation across two distinct endothelial agonists suggests that chronic SCI is associated with endothelial dysfunction not confined to a specific receptor or intracellular signaling pathway. Moreover, oxidative stress is a contributing factor underlying SCI-related endothelial vasodilator dysfunction. NCT06443151 CLINICAL PERSPECTIVEO_LIThe novel finding of this study is that individuals with SCI demonstrate impaired endothelial vasodilator function in absence of traditional cardiovascular risk factors. C_LIO_LIOxidative stress is a contributing factor to SCI-related endothelial vasodilator dysfunction. C_LIO_LIFuture studies are needed to determine the efficacy of therapeutic interventions, either lifestyle or pharmacologic, in improving endothelial function in order to mitigate the elevated ASCVD risk after SCI. C_LI

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Park, A. J., DeSouza, C. A., Madera, G., Morey, C., Summers, M., Garcia, V. P., Berry, A. R., Ruzenne, S. T., DeSouza, N., Holzer, J. P., Deitemeyer, A., Greiner, J. J., Stauffer, B. L.. 2026-05-30. Endothelium-Dependent Vasodilation is Impaired in Chronic Spinal Cord Injury and is Associated with Oxidative Stress. https://doi.org/10.64898/2026.05.27.728335

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