Effects of aldose reductase inhibitor on microneurographically assessed peripheral sympathetic nerve activity in rats

- Aldose reductase inhibitor (ARI) is expected to treat diabetic neuropathy.
- We assessed sympathetic nerve activity microneurographically in ARI-treated rats.
- ARI prevented reduction of action potential rate and incidence in diabetic rats.
- Action potential rate and incidence can be a useful indicator of diabetic neuropathy.

Autonomic neuropathy, one of the serious complications of diabetes, decreases quality of life. Aldose reductase inhibitor (ARI) blocks sorbitol production, and results in prevention of damage of nerve fibers. Beneficial effects of ARI have usually been confirmed through nerve conduction velocity tests in motor and sensory nerves. On the other hand, few reports have dealt with the effects of ARI on the small fiber activity such as sympathetic nerve one. In the present study, we administered eparlestat, ARI orally for 3 weeks, to streptozotocin-induced diabetic (STZ + ARI) rats, and then recorded peripheral sympathetic nervous signal detected with microneurographic technique. Action potentials (APs) and bursts of APs were detected from the recorded signal, and their rates and incidences (= rates/heart rate) were compared with those in non-diabetic control (normal) and ARI-untreated streptozotocin-induced diabetic (STZ) rats. While streptozotocin and/or epalrestat did not influence burst parameters in all the three groups, AP parameters in the STZ + ARI and normal groups were higher than those in the STZ group. However, response of AP parameters to the intravenous glucose administration (IVGA) was not large in the STZ + ARI group, similar to that of the STZ group and different from that of the normal group in which AP parameters increased after IVGA. The results suggest that epalrestat may prevent sympathetic nerve activity (SNA) from reduction under hyperglycemic and insulin-depleted conditions, that enhancement of SNA was not induced after IVGA under that condition, and that AP parameters might be useful to assess the degree of neuropathy.