Application of angiotensin II to healthy rat sciatic nerve can produce neuropathy without associated vasculopathy.

Elevated angiotensin II (AII) levels have been associated with hypertension, diabetes, and polyneuropathy. It is unknown whether AII applied to healthy nerve can be used to model a confined neuronal injury by producing localized vasculopathy and associated neuropathy. In this study, angiotensin II (2.2 μg/ml) or saline was infused constantly via osmotic pump onto the sciatic nerve of 20 rats for 12 weeks. Nerve conduction studies were repeated every 4 weeks, and sciatic nerve was collected for pathological analysis at 12 weeks. Animals infused with AII showed a significant decrease in nerve fiber diameter (P < 0.001), axon diameter (P < 0.001), and myelin thickness (P < 0.001), despite the absence of electrophysiological changes. Surprisingly, there was no significant difference in vessel diameter or wall thickness. AII can cause structural alterations in healthy nerve without associated changes in vasculature, implying the existence of additional previously unrecognized mechanisms of AII-induced neuronal injury.