Effect of zenarestat, an aldose reductase inhibitor, on endoneurial blood flow in experimental diabetic neuropathy of rat

The effects of zenarestat, an aldose reductase inhibitor, on endoneurial bl ood flow (NBF) were explored in streptozotocin-induced diabetic rats. Rats were maintained on a diet of containing 0.09% zenarestat for 8 weeks, then NBF in the sciatic nerve was measured using microelectrode hydrogen polarog raphy. NBF in the diabetic control rats was significantly lower than values in age-matched control rats, however, NBF was not significantly altered in diabetic rats treated with zenarestat. Direct application of nitric oxide synthase inhibitor, NG-nitro-L-arginine, did not affect NBF in diabetic con trol rats, whereas this application significantly reduced NBF both in age-m atched control and zenarestat treated diabetic rats. Considerable levels of zenarestat were confirmed in the sciatic nerve in the drug treated rats. T hese data suggest that aldose reductase, such as zenarestat, might restore or prevent the alteration of endoneurial blood flow resulting from an impai rment of nitric oxide function. (C) 2001 Elsevier Science Ireland Ltd. All rights reserved.