Inhibition of prostacyclin and thromboxane A₂ generation by low-dose aspirin at the site of plug formation in man in vivo

In a double-blind placebo-controlled crossover study, we investigated in seven healthy male volunteers the effect of a low-dose aspirin regimen (35 mg acetylsalicylate per day for 7 days) on the formation of thromboxane A₂ (TxA₂) and prostacyclin (PGI₂) in blood emerging from a standardized injury of the microvasculature made to determine skin bleeding time. When subjects were treated with placebo, there was rapid and substantial generation of TxA₂ and PGI₂ at the site of platelet-vessel wall interaction within the first 2 min after vascular injury. This was reflected by a greater than 100-fold and greater than 10-fold increase in thromboxane B₂ (TxB₂) and 6-keto-prostaglandin F, a (6-keto- PGF, a) in blood obtained from incisions made to determine bleeding time as compared with the corresponding plasma values. Low-dose aspirin caused a significant inhibition of both TxA₂ and PGO₂ generation in blood sampled from the skin incisions, represented by a 85% and 92% and 81% and 84% inhibition of TxB₂ and 6-keto-PGFIa, respectively, as compared with controls. We therefore conclude that (1) rapid activation of both platelet prostaglandin metabolism and vascular PGO2 biosynthesis occurs at the site of platelet-vessel wall interaction, and (2) low-dose aspirin results in a significant inhibition of both platelet and vascular cyclooxygenase activity. Thus, our data fail to confirm the concept of a differential effect of low-dose aspirin on platelet and vascular prostaglandin synthesis in man in vivo.