Selective Inhibition of Thromboxane Synthetase with Dazoxiben - Basis of Its Inhibitory Effect on Platelet Adhesion

V C Menys; J A Davies

doi:10.1055/s-0038-1657330

Thrombosis and Haemostasis, Table of Contents

Thromb Haemost 1983; 49(02): 096-101
DOI: 10.1055/s-0038-1657330

Original Article

Schattauer GmbH Stuttgart

Selective Inhibition of Thromboxane Synthetase with Dazoxiben - Basis of Its Inhibitory Effect on Platelet Adhesion

V C Menys

The University Department of Medicine, The General Infirmary, Leeds, England

,

J A Davies

The University Department of Medicine, The General Infirmary, Leeds, England

› Author Affiliations

Abstract

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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-PGF_lα 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-PGFi_α. 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 A₂ - Prostacyclin - Prostaglandin endoperoxides

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References

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