ALTERATION IN THE BALANCE OF PROSTAGLANDIN AND THROMBOXANE SYNTHESIS IN DIABETIC RATS

Abstract

An evaluation of platelet and vascular (aortic) arachidonic acid metabolism was performed in Lewis male rats rendered diabetic by streptozotocin injection and the results were compared to those in matched controls. Parameters evaluated included the release of this fatty acid from prelabeled platelets and aortas and conversion of labeled fatty acid to thromboxane B2 and 6-keto-PG[prostaglandin]F1.alpha. in platelets and aortas, respectively. Diabetic rat platelets showed markedly increased release of arachidonic acid with thrombin used as the aggregating stimulus. Conversion of arachidonic acid to thromboxane B2 was slightly, but not significantly, higher in the diabetic rats. In the vessel, thrombin-stimulated release of arachidonic acid was slightly, but not significantly, increased in the diabetic animals when compared to controls. This finding was associated with a decrease in vascular production of 6-keto-PGF1.alpha. both in vascular tissues incubated with arachidonic acid alone and in vascular tissues incubated with thrombin. The changes observed in both platelet and vascular metabolism of arachidonic acid were corrected by islet tissue transplantation, suggesting a disease-specific effect. The changes observed in arachidonic acid metabolism suggest a significant imbalance in thromboxane A2 and PGI2 production in diabetic rats. Such changes might promote the development of the microvascular changes seen in diabetes mellitus.