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The effects of antiplatelet agents on the disorders of lipid and arachidonic acid (AA) metabolism were studied in hypercholesteromic rats (HC). HC rats received an atherogenic diet (containing 2% cholesterol, 0.5% cholic acid, 10% lard, 5% cane sugar, 0.2% methylthiouracil, and 82.3% basal diet) for 6 weeks, 350, 000units/kg of vitamin D2, and also olieve oil (5ml/kg) for 4 days. Antiplatelet agents, OKY 046 and ONO 3144, were administered to HC rats (100mg/kg/day). After 6 weeks, plasma lipids were measured by conventional methods, and both TXA2 generation in the platelet and PGI2 generation in the isolated aorta were measured by RIA.The results were as follows: 1) Plasma cholesterol, triglyceride and β-lipoprotein were increased in HC rats. 2) Vascular UGI2 generation was decreased, and AA induced platelet TXA2 generation, and TXA2/PGI2 induced by collagen or AA were elevated in HC rats, while platelet TXA2 generation and TXA2/PGI2 were decreased in OKY and ONO treated HC rats, 3) Atherosclerotic changes in intima and media were observed in 5/12 HC rats, 1/6 OKY treated HC rats and none of 4 ONO treated HC rats.These results might suggest that vascular PGI2 generation was decreased and platelet TXA2 generation was increased in these experimental atherosclerotic rats, however the administration of antiplatelet agents OKY 046 and ONO 3144 seemed to prevent atherosclerosis through the repairment of AA metabolism.

Effects of antiplatelet agents on platelet TXA2 and vascular PGI2 generation in cholesterol fed rats.