Summary
Platelet adhesion to rabbit aortic subendothelium or collagen-coated glass was quantitated
in a rotating probe device by uptake of radio-labelled platelets. Under conditions
in which aspirin had no effect, dazoxiben, a selective inhibitor of thromboxane synthetase,
reduced platelet adhesion to aortic subendothelium by about 40% but did not affect
adhesion to collagen-coated glass. Pre-treatment of aortic segments with 15-HPETE,
a selective inhibitor of PGI2-synthetase, abolished the inhibitory effect of dazoxiben on adhesion. Concentrations
of 6-oxo-PGFlα in the perfusate were raised in the presence of dazoxiben alone, and following addition
of thrombin (10 units/ml) there was a 2-3 fold increase in concentration. Perfusion
of damaged aorta with platelets labelled with (14C)-arachidonic acid in the presence of thrombin and dazoxiben resulted in the appearance
of (14C)-labelled-6-oxo-PGFiα. Inhibition of thromboxane synthetase limits platelet adhesion probably by promoting
vascular synthesis of PGI2 from endoperoxides liberated from adherent platelets, which subsequently promotes
detachment of cells from the surface.
Keywords
Platelet adhesion - Dazoxiben - Thromboxane A
2
- Prostacyclin - Prostaglandin endoperoxides
