Effect of Treating Streptozotocin-Induced Diabetic Rats With Sorbinil Myo-Inositol or Aminoguanidine on Endoneurial Blood Flow Motor Nerve Conduction Velocity and Vascular Function of Epineurial Arterioles of the Sciatic Nerve

摘要

Previously we have demonstrated that diabetes causes impairment in vascular function of epineurial vessels, which precedes the slowing of motor nerve conduction velocity. Treatment of diabetic rats with aldose reductase inhibitors, aminoguanidine or myo-inositol supplementation have been shown to improve motor nerve conduction velocity and/or decreased endoneurial blood flow. However, the effect these treatments have on vascular reactivity of epineurial vessels of the sciatic nerve is unknown. In these studies we examined the effect of treating streptozotocininduced rats with sorbinil, aminoguanidine or myo-inositol on motor nerve conduction velocity, endoneurial blood flow and endothelium dependent vascular relaxation of arterioles thatprovide circulation to the region of the sciaticnerve. Treating diabetic rats with sorbinil,aminoguanidine or myo-inositol improved thereduction of endoneurial blood flow and motornerve conduction velocity. However, onlysorbinil treatment significantly improved thediabetes-induced impairment of acetylcholinemediatedvasodilation of epineurial vessels ofthe sciatic nerve. All three treatments were efficaciousin preventing the appropriate metabolicderangements associated with either activationof the polyol pathway or increased nonenzymaticglycation. In addition, sorbinil wasshown to prevent the diabetes-induced decreasein lens glutathione level. However, other markers of oxidative stress were not vividlyimproved by these treatments. These studiessuggest that sorbinil treatment may be moreeffective in preventing neural dysfunction indiabetes than either aminoguanidine or myoinositol.