AN ALDOSE REDUCTASE INHIBITOR, TAT, REDUCES ADP-INDUCED PLATELET HYPERAGGREGATION IN STREPTOZOTOCIN-INDUCED DIABETIC RATS WITH NEUROPATHY

To investigate the relationship between metabolic and vascular factors , especially polyol pathway and platelet aggregation, in the pathogene sis of diabetic neuropathy, the effects of a novel potent aldose reduc tase inhibitor, TAT ((5-(3-thienyl)tetrazol-1-yl) acetic acid monohydr ate) on adenosine diphosphate-induced platelet aggregation, polyol con tents in platelets, motor nerve conduction velocity (MNCV), and sciati c nerve blood flow (SNBF) were examined in streptozotocin-induced diab etic rats, Diabetic rats demonstrated hyperaggregation in response to adenosine diphosphate, accompanied by sorbitol and fructose accumulati on and myoinositol depletion in platelets, Treatment with TAT improved these abnormalities in diabetic rats, A delayed MNCV and a reduced SN BF in diabetic rats were normalized by the administration of TAT, Thes e observations suggest that increased polyol pathway activity plays an important role in platelet aggregation in the development of diabetic neuropathy and that aldose reductase inhibitor is useful for the trea tment of diabetic neuropathy from the viewpoint not only of metabolic factors but also of vascular factors.