Effects of aspirin dosage and time of administration on arterial prostacyclin production and platelet aggregation in rats.
Previously we reported that electrically-induced carotid artery thrombosis in anesthetized rats was prevented by 3.3 or 10 mg/kg aspirin (ASA) given i.v. 10 min before injury but not by 1.7, 20 or 100 mg/kg and protection was lost by delaying injury to 20 min (Haemostasis 13:42, 1983). Here, collagen-induced platelet aggregation and arterial prostacyclin-generating activity, measured by RIA for 6 keto-PGF1 alpha and by human platelet aggregation bioassay, were studied ex vivo after i.v. ASA to anesthetized rats. In all cases where platelet aggregation was inhibited less than 50%, no protection had been observed (1.7 mg/kg at 10 min, 3.3 at 20 min, 20 at 10 min). In the two cases where protection had been observed, platelet aggregation was inhibited by about 75% or more and in one, prostacyclin activity was about 50% of normal (3.3 mg/kg at 10 min). Thus in five of six dose-time combinations tested, antithrombotic protection could be explained by a requirement for about 50% of normal prostacyclin activity and about 75% of inhibition of collagen aggregation. Aberrant findings are discussed in the light of knowledge of salicylate/aspirin competition for cyclooxygenase.
D000818:Animals; D001158:Arteries / Q000187:drug effects* / Q000378:metabolism; D001241:Aspirin / Q000008:administration & dosage / Q000494:pharmacology*; D001681:Biological Assay; D003094:Collagen / Q000494:pharmacology; D004334:Drug Administration Schedule; D011464:Epoprostenol / Q000096:biosynthesis*; D008297:Male; D010974:Platelet Aggregation / Q000187:drug effects*; D011863:Radioimmunoassay; D051381:Rats; D013927:Thrombosis / Q000517:prevention & control
D003094:Collagen; D011464:Epoprostenol; D001241:Aspirin