Diabetes
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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. ⋯ 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.