Abstract
Thromboxane A2 (TxA2) and prostacycline (PGI2) are two novel prostaglandin (PG)-like substances which are derived from arachidonic acid via PG endoperoxides (PGG2 and PGH2). TxA2 is a potent labile platelet aggregator and vascular constrictor, whereas PGI2 is a potent labile antithrombotic compound and vasodilator.
In the present work we investigated the effect of thromboxane synthetase inhibitors, OKY-046 and OKY-1580, on the action of bronchoactive agents in guinea pig tracheal strips, and on arachidonic acid metabolism through isolated perfused guinea pig lung lobes.
1) OKY-046 and OKY-1580 attenuated histamine-, serotonin-, acetylcholine-, bradykinin- and PGF2α-induced contractile responses in guinea tracheal strips dose-dependently.
2) OKY-046 and OKY-1580 potentiated isoproterenol, salbutamol and PGE2-induced relaxation responses in guinea pig tracheal strips dose-dependently.
3) OKY-046 and OKY-1580 inhibited the biosynthesis of TxA2 and accelerated the production of 6-keto PGF1α from arachidonic acid through isolated perfused guinea pig lung lobes.
The above results suggest that OKY-046 and OKY-1580 might become useful therapeutic agents for the treatment of pulmonary thromboembolism and chronic obstructive lung diseases.
