ラット大動脈からの Prostacyclin (PGI<sub>2</sub>) 放出に関する検討

Abstract

Owing to the depelopment of Prostaglandin reserch, it has been known that the endothelial cell of blood vessels generate prostacyclin (PGI2) which is protective for platelet aggregation and vasoconstriction.On the other hand, Thromboxane A2 (TXA2) is a powerful stimulant of platelet aggregation and vasoconstriction. Both PGI2 and TXA2 are the derivatives from the prostaglandin endoperoxides PGG2 and PGH2.It was also reported that these substances play an important role in the developement of cardiovascular disease.In this report we investigated the effect of antiplatelet aggregating and vasoactive agents of PGI2 release from rat aorta.PGI2 activity was assayed by the inhibitory effect on ADP-induced platelet aggregation. Thoracic aorta was isolated from 200g male wistar rat under pentobarbital anesthesia and cut into rings. The aortic rings were kept in cold KRP buffer and used for the experiment within 40min. The aortic ring was incubated in 0.5ml of 0.05M Tris HCl buffer (pH 7.5) per 1mg aortic ring at room temperature for 10min. Aliquot of this incubation medium (50μl) was added into 0.3ml of human PRP (Platelet Rich Plasma, count 300.000/mm3) and then incubated at 37°C for 2min. and ADP induced aggregation was evaluated.When the aortic ring was incubated in the medium containing Dipyridamole (50 and 100μ/ml) or Trapymin (50 and 100μg/ml), PGI2 release from aortic ring was significantly accelerated. The accelation of PGI2 generation was inhibited by the preincubation of Indomethacin (11.5μg/ml).Moreover, the aorta of rat intravenously injected with these agents (Dipyridamole 25mg/kg and Trapymin 30mg/kg) was incubated in the same condition. PGI2 release was significantly increased in the aorta of rats injected with the agents as described above.This PGI2 generation were inhibited in the aorta of rats previously injected with Indomethacin (3.57mg/kg).These agents have been established as the inhibitory agents for the platelet aggregation. As demonstrated in this paper, it is noteworthy that these agents have potentiating activity in the PGI2 generation from the arterial wall.