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 F1 alpha (6-keto-PGF1 alpha) 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 PGI2 generation in blood sampled from the skin incisions, represented by a 85% and 92% and 81% and 84% inhibition of TxB2 and 6-keto-PGF1 alpha, respectively, as compared with controls. We therefore conclude that rapid activation of both platelet prostaglandin metabolism and vascular PGI2 biosynthesis occurs at the site of platelet-vessel wall interaction, and 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.
D015121:6-Ketoprostaglandin F1 alpha / Q000097:blood; D000328:Adult; D001241:Aspirin / Q000008:administration & dosage / Q000494:pharmacology*; D001760:Bleeding Time; D001792:Blood Platelets / Q000187:drug effects; D001808:Blood Vessels / Q000187:drug effects; D004311:Double-Blind Method; D011464:Epoprostenol / Q000037:antagonists & inhibitors*; D006487:Hemostasis / Q000187:drug effects*; D006801:Humans; D008297:Male; D013927:Thrombosis / Q000517:prevention & control; D013928:Thromboxane A2 / Q000037:antagonists & inhibitors*; D013929:Thromboxane B2 / Q000097:blood
D013929:Thromboxane B2; D013928:Thromboxane A2; D015121:6-Ketoprostaglandin F1 alpha; D011464:Epoprostenol; D001241:Aspirin