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 pathogenesis of diabetic neuropathy, the effects of a novel potent aldose reductase inhibitor, TAT ((5-(3-thienyl) tetrazol-1-yl) acetic acid monohydrate) on adenosine diphosphate-induced platelet aggregation, polyol contents in platelets, motor nerve conduction velocity (MNCV), and sciatic nerve blood flow (SNBF) were examined in streptozotocin-induced diabetic rats. Diabetic rats demonstrated hyperaggregation in response to adenosine diphosphate, accompanied by sorbitol and fructose accumulation and myoinositol depletion in platelets. Treatment with TAT improved these abnormalities in diabetic rats. A delayed MNCV and a reduced SNBF in diabetic rats were normalized by the administration of TAT. These 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 treatment of diabetic neuropathy from the viewpoint not only of metabolic factors but also of vascular factors.
D000244:Adenosine Diphosphate / Q000502:physiology; D000449:Aldehyde Reductase / Q000037:antagonists & inhibitors*; D000665:Ampholyte Mixtures / Q000378:metabolism; D000818:Animals; D001786:Blood Glucose / Q000187:drug effects; D001792:Blood Platelets / Q000737:chemistry; D003921:Diabetes Mellitus, Experimental / Q000150:complications / Q000503:physiopathology*; D003929:Diabetic Neuropathies / Q000188:drug therapy* / Q000209:etiology; D004791:Enzyme Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D008297:Male; D009431:Neural Conduction / Q000187:drug effects / Q000502:physiology; D010974:Platelet Aggregation / Q000187:drug effects*; D011108:Polymers / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D012584:Sciatic Nerve / Q000098:blood supply; D013311:Streptozocin; D013777:Tetrazoles / Q000494:pharmacology* / Q000627:therapeutic use; D013876:Thiophenes / Q000494:pharmacology* / Q000627:therapeutic use
D000665:Ampholyte Mixtures; D001786:Blood Glucose; D004791:Enzyme Inhibitors; D011108:Polymers; D013777:Tetrazoles; D013876:Thiophenes; C024617:polyol; C080974:(5-(3-thienyl)tetrazol-1-yl)acetic acid; D013311:Streptozocin; D000244:Adenosine Diphosphate; D000449:Aldehyde Reductase