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 diabetescauses impairment in vascular function ofepineurial vessels, which precedes the slowingof motor nerve conduction velocity. Treatmentof diabetic rats with aldose reductaseinhibitors, aminoguanidine or myo-inositolsupplementation have been shown to improvemotor nerve conduction velocity and/ordecreased endoneurial blood flow. However,the effect these treatments have on vascularreactivity of epineurial vessels of the sciaticnerve is unknown. In these studies we examinedthe effect of treating streptozotocininducedrats with sorbinil, aminoguanidine ormyo-inositol on motor nerve conduction velocity,endoneurial blood flow and endothelium dependentvascular 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.