Effect of prostaglandin synthetase inhibitors on platelet aggregation and thromboxane production in diabetes mellitus.
Platelet aggregation is known to be increased in diabetes mellitus, and the enhanced thromboxane production has been shown to be one of the causes of such abnormal platelet function. To investigate which step is activated in diabetic prostaglandin metabolism, three specific inhibitors of prostaglandin synthetases were used in this study, which were mepacrine, indomethacin and imidazole. Platelet aggregation induced by collagen was significantly increased accompanying enhanced thromboxane production in diabetics with proliferative retinopathy compared with age matched controls. Platelet aggregation in diabetics with proliferative retinopathy was less inhibited by the addition of each inhibitor compared with controls. However, there was no difference in inhibitory pattern of platelet aggregation among the three inhibitors. In addition, thromboxane production during aggregation in diabetics with proliferative retinopathy was significantly greater than that in controls by the addition of each inhibitor. Inhibitory patterns of thromboxane production did not differ among the addition of three inhibitors. It is concluded that enhanced thromboxane production resulting in enhanced platelet aggregation would be related to diabetic vascular complications. This abnormal prostaglandin production can be due to the activation of general steps in prostaglandin metabolism in diabetic platelets, not of a specific enzyme.
D000328:Adult; D003920:Diabetes Mellitus / Q000097:blood*; D003930:Diabetic Retinopathy / Q000097:blood*; D005260:Female; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology; D007213:Indomethacin / Q000494:pharmacology; D008297:Male; D008875:Middle Aged; D010974:Platelet Aggregation / Q000187:drug effects; D011796:Quinacrine / Q000494:pharmacology; D013929:Thromboxane B2 / Q000096:biosynthesis*; D013931:Thromboxanes / Q000096:biosynthesis*
D007093:Imidazoles; D013931:Thromboxanes; D013929:Thromboxane B2; C029899:imidazole; D011796:Quinacrine; D007213:Indomethacin