Prostacyclic production in rabbit arteries in situ: Inhibition by arachidonic acid-induced endothelial cell damage or by low-dose aspirin

The central artery of the rabbit ear was perfused in situ and effluent fractions from the artery were assayed for 6-keto-prostaglandin F_1α (6-K-PGF_1α) and thromboxane B₂ (TxB₂), the stable metabolites of prostacyclin (PGI₂) and TxA₂, using specific radioimmunoassays. These metabolites of arachidonic acid (AA) were not detected in the effluent during infusion of Tyrode's solution but both metabolites were detected when small amounts of AA were infused into the artery. Examination of the arteries by scanning electron microscopy revealed that high concentrations of AA which caused a short burst of 6-K-PGF_1α and TxB₂ production damaged the endothelial cells while lower concentrations which stimulated continuous production did not cause damage. When a non-damaging concentration of AA was infused into an artery that the previously received a damaging concentration, PG production was greatly reduced. Pretreatment of the rabbits with 4 mg/kg acetyl-salicyclic acid (ASA) inhibited 6-K-PGF_1α production by the rabbit ear artery in response to AA and 70% inhibition was still evident 18 hours after ASA.