UBC Theses and Dissertations
Above and below : changes in conduit artery after spinal cord injury, autonomic dysreflexia, and passive exercise Zheng, Mei Mu Zi (Annie)
Spinal cord injury (SCI) is a devastating condition that not only results in motor and sensory loss, but also autonomic dysfunctions. Individuals with SCI experience a 3-4 fold increased risk of cardiovascular disease (CVD), the leading cause of mortality in this population. Endothelial dysfunction is among the earliest markers of CVD progression. This thesis aims to: 1) clarify previous reports showing a counterintuitive improvement in endothelial function after SCI, 2) examine the effect of autonomic dysreflexia (AD) on conduit vasculature, and 3) assess the efficacy of passive exercise (PE) to reverse vascular dysfunction. In uninjured controls (CON), T3-complete spinal cord transected Wistar rats (SCI), T3-transected with induced AD by colorectal distension (SCI+CRD), and T3-transected with PE (SCI+PE), we assessed endothelium-dependent vasodilation and specific mechanisms for relaxation in brachial (BA) and femoral artery (FA) using wire-myography. Sympathetic innervation, mechanotransducer expression [transient receptor potential channel V4 (TRPV4)], arterial morphology, and profibrotic markers were assessed using immunohistochemistry. Impaired reactivity to acetylcholine was seen in FA after SCI via decreased contribution of endothelium dependent hyperpolarizing factor (EDHF) mediated pathways, while BA showed preserved endothelial function. Moreover, FA in SCI exhibited inward remodelling, 37.7% less sympathetic nerve fiber density, and increased collagen I expression (53.0%). Chronic repetitive AD resulted in a shift in vasodilatory mechanisms away from nitric oxide and towards EDHF, hypersensitivity to phenylephrine, and reduced elastin expression (13.9%). Passive hind-limb exercise after SCI led to improved sensitivity of FA to acetylcholine, through an increase in TRPV4 and prostacyclin-mediated pathways for vasodilation. Outward remodelling, as well as decreased expression of transforming growth factor beta (47.7%) and collagen I (39.0%) was seen in FA after PE. We have shown, for the first time, the expected endothelial dysfunction in the inactive/supraspinally disrupted FA after SCI and that chronic repetitive AD resulted in exacerbation of vascular dysfunction caudal to injury. Furthermore, PE was effective in reversing endothelial dysfunction and provided atheroprotective benefit, indicating PE may be a viable therapeutic intervention for preventing CVD after SCI. The observed changes provide insight into the mechanisms of endothelial dysfunction and possible directions on improvement of vascular health after SCI.
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