Incomplete Inhibition of Platelet Secretion by Low-dose Aspirin.
This study determines the effects of low-dose oral acetylsalicylic acid (Aspirin) on platelet aggregation and dense granule secretion in relation to inhibition of thromboxane formation. In addition, possible modifications of inhibition of platelet function by iloprost and linsidomine (SIN-1) were also studied. Aspirin (40 mg/day) was administered to 15 healthy male non-smoking volunteers for 8 consecutive days. Platelet function was measured ex vivo before and 12 h after the last drug intake. At the same times urinary excretion of thromboxane B(2) (TXB(2)) and 6-oxo-PGF(1α) were determined. Asirin treatment resulted in a significant (P < 0.01), by 65%, reduction of urinary TX B(2) excretion, whereas urinary excretion of 6-oxo-PGF(1α) remained unchanged, demonstrating the expected selectivity of low-dose aspirin for the platelet cyclooxygenase. There was also a nearly complete (93-95%) inhibition of collagen (0.3-5 μg/ml)-induced thromboxane formation in platelets. However, collagen-induced ATP-and 5-HT secretion was much less inhibited by aspirin and was reduced by only 20% at 5 μg/ml collagen. Similar results were obtained with ADP while thrombin (> 1.2 IU/ml)-induced 5-HT secretion was not antagonized at all. Also aspirin did not affect the inhibition of platelet function by iloprost and linsidomine (SIN-1). It is concluded that stimulation of platelet secretion by stronger stimuli, such as collagen or thrombin, is largely cyclooxygenase-independent and may not be detected by measuring serum thromboxane levels. This may be relevant for clinical situations with shear-stress-induced platelet activation, for example at carotis stenoses or other types of atherosclerotic plaques.
Institut für Pharmakologie. Heinrich-Heine-Universität, Moorenstrasse 5, D-40225, Düsseldorf, Germany.
M
M
Braun
J
J
Kramann
H
H
Strobach
K
K
Schrör