Superimposition of hypertension on diabetic peripheral neuropathy affects small unmyelinated sensory nerves in the skin and myelinated tibial and sural nerves in rats with alloxan-induced type 1 diabetes

Diabetic peripheral neuropathy (DPN) is a major complication of diabetes mellitus, and hypertension is considered to be a risk factor for DPN in patients with type 1 diabetes (T1DM). However, the morphological effects of hypertension on DPN are unclear. In this study, we investigated the effect of hypertension on DPN by investigating the changes in unmyelinated and myelinated nerve fibers in hypertensive rats with alloxan (AL)-induced T1DM. Thirteen-week-old WBN/Kob rats with AL-induced diabetes were allocated to receive tap water only (AL group), tap water containing 0.5% saline (0.5AN group), or tap water containing 0.75% saline (0.75AN group) for 15 weeks. Hyperglycemia was maintained for 15 weeks, and the animals were euthanized at 28 weeks. By 23 weeks of age, the systolic blood pressure was significantly higher in the 0.75AN and 0.5AN groups than in the AL group and was unchanged in all groups at 28 weeks. The number of intraepidermal sensory unmyelinated nerve fibers was significantly smaller in the 0.75AN and 0.5AN groups than in the AL group. The axonal size in the myelinated tibial and sural nerve fibers was significantly smaller in the 0.75AN group than in the AL group. Furthermore, luminal narrowing and endothelial hypertrophy were observed in the endoneurial tibial nerve vessels in the 0.75AN group. These findings suggest that superimposing hypertension on hyperglycemia may accelerate a reduction in the number of small unmyelinated sensory nerve fibers in the skin and induce mild axonal atrophy in myelinated tibial and sural nerve fibers in rats with AL-induced T1DM.