Sensitivity of rabbit platelet and aortic cyclooxygenase to inhibition by aspirin
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It has been suggested that aspirin (ASA) would be more effective as an antithrombotic agent if employed in a dose which inhibits platelet thromboxane synthesis selectively, sparing vascular synthesis of prostaglandin I2 (PGI2). We have studied the effect of ASA concentration on rabbit platelet and aortic cyclooxygenase activity in vitro and the effect of administration of varying doses of ASA to rabbits on the cyclooxygenase activity of these tissues ex vivo. We also measured plasma levels of thromboxane B2 (TXB2) and 6-keto-prostaglandin F1 alpha (6-keto-PGF1 alpha) after infusion of arachidonic acid into rabbits pretreated with varying doses of ASA. Concentrations or doses of ASA required for 50% inhibition were about 10 times greater for the arterial enzyme than for the platelet enzyme in the in vitro and ex vivo studies. However, the dose required for complete inhibition of the platelet enzyme was 1 mg/kg and this dose inhibited the vascular enzyme by 62%. We conclude that meaningful selective inhibition of cyclooxygenase activity of the two tissues is difficult to achieve in the rabbit. Since doses of ASA which are antithrombotic appear to be high enough to almost totally inhibit vascular PGI2 synthesis, PGI2 synthesis may be a relatively unimportant mechanism for prevention of thrombosis.
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