ACETYLSALICYLIC ACID: INHIBITION OF PLATELET AGGREGATION IN THE RABBIT

¹ Department of Pharmacology, Sterling-Winthrop Research Institute, Rensselaer, New York

Acetylsalicylic acid (ASA) inhibits the aggregation of platelets induced by collagen in rabbit plasma enriched with platelets. Extent of the inhibition is related both to incubation time and concentration of ASA. Salicylic acid is 50 to 100 times less potent than ASA, and inhibition by salicylic acid is independent of incubation time. Repeated washing and resuspension of the platelets after incubation with ASA does not reverse the ASA effect, whereas salicylic acid inhibition is abolished by washing. ASA inhibition of aggregation is related to acetylation of the platelet, a process different from acetate uptake. These two processes can be differentiated in three ways. 1) Platelet suspensions incubated with ³H-NaAc take up large quantities of acetate, but their ability to aggregate is unaffected. 2) Studies of lipid and protein distributions in platelets incubated with either ³H-acetyl ASA or ³H-NaAc demonstrate that ³H-acetyl ASA labels protein to a significantly greater degree than does ³H-NaAc, whereas ³H-NaAc labels the lipid fraction more extensively than does ³H-acetyl ASA. 3) Acetate uptake, but not protein acetylation, is blocked by addition of tetramethyleneglutaic anhydride to the incubate. Only 10% of the total platelet acetylation can be accounted for by a plasma intermediary. It is concluded that acetylsalicylic acid acetylates platelets directly and that this acetylation is related to inhibition of platelet aggregation. ASA inhibits platelet aggregation when given in vivo as well as in vitro.

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