Endothelin-1 (ET) is a potent vasoconstrictor of vasa nervorum, the vascular supply of peripheral nerve trunks, that may, through elevated circulating levels, promote microangiopathy in human diabetes patients. In previous work, we observed that sciatic nerve trunks of rats exposed to epineurial ET developed transient dose-dependent endoneurial ischemia that might be associated with reversible motor conduction block. In the present study, we explored the possibility that ET ischemia might selectively damage axons of diabetic nerve trunks. We exposed the sciatic nerves of rats with streptozotocin-induced diabetes of 6–8 weeks duration and age-matched nondiabetic controls to supramaximal vasoconstrictive concentrations of epineurial ET and studied serial regional erythrocyte flux (laser Doppler flowmeter) and sciatic tibial motor conduction for up to 14 days. In diabetic rats, but not controls, ET ischemia damaged a large proportion of sciatic axons, predicted in each instance by focal motor conduction block across the site of ET application and eventual loss of distal motor nerve excitability. Histological studies confirmed the presence of severe axonal degeneration in diabetic sciatic nerves exposed to ET. Part of the susceptibility to ET in diabetes was accounted for by more intense and prolonged vasoconstriction. Diabetic nerves are selectively susceptible to ET-mediated ischemia.
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Original Articles| May 01 1996
Diabetes Increases Sciatic Nerve Susceptibility to Endothelin-Induced Ischemia
Douglas W Zochodne;
Address correspondence and reprint requests to Dr. D.W. Zochodne, University of Calgary, Department of Clinical Neurosciences, Room 182A, 3330 Hospital Dr., N.E., Calgary, Alberta T2N 4N1, Canada. E-mail: email@example.com.
Douglas W Zochodne, Chu Cheng, Hong Sun; Diabetes Increases Sciatic Nerve Susceptibility to Endothelin-Induced Ischemia. Diabetes 1 May 1996; 45 (5): 627–632. https://doi.org/10.2337/diab.45.5.627
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