Effects of a thromboxane A2-receptor antagonist, a thromboxane synthetase inhibitor and aspirin on prostaglandin I2 production in endothelium-intact and -injured aorta of guinea pigs.
We examined the effects of KW-3635, a thromboxane (TX) A2-receptor antagonist, and OKY-046, a TX synthetase inhibitor, on the prostaglandin (PG) I2 production in endothelium-intact and -injured guinea pig aorta and compared them with those of aspirin. In the endothelium-intact aorta, both the low (3 mg/kg) and the high (100 mg/kg) dose of aspirin similarly reduced the PGI2 production, as measured ex vivo 1 hr after the injury. In contrast, neither KW-3635 (10 mg/kg) nor OKY-046 (30 mg/kg) inhibited the PGI2 production. The endothelial injury, induced by balloon catheterization, caused a reduction of PGI2 production in the aorta and decline of plasma PGI2/TXA2 ratio. In the endothelium-injured animals, the high dose of aspirin further reduced the PGI2 production in the aorta, whereas KW-3635 and OKY-046 did not affect it. KW-3635 and OKY-046 also ameliorated the reduced ratio of PGI2/TXA2 in the plasma. The present results demonstrate that aspirin, but not KW-3635 or OKY-046, reduces the PGI2 production in the aorta either in the endothelium-intact or -injured state. It is thus suggested that the TXA2-receptor antagonist and the TX synthetase inhibitor have some advantages over aspirin when used for the prevention of acute thrombosis after percutaneous transluminal angioplasty.
Higo
K
K
Department of Pharmacology, Kyowa Hakko Kogyo Co., Ltd., Shizuoka, Japan.
Karasawa
A
A
D000800:Angioplasty, Balloon; D000818:Animals; D001013:Aorta, Thoracic / Q000293:injuries / Q000378:metabolism*; D001241:Aspirin / Q000494:pharmacology*; D001562:Benzimidazoles / Q000494:pharmacology; D001584:Benzoxepins / Q000494:pharmacology; D004730:Endothelium, Vascular / Q000378:metabolism*; D011464:Epoprostenol / Q000096:biosynthesis*; D006168:Guinea Pigs; D066298:In Vitro Techniques; D008297:Male; D008689:Methacrylates / Q000494:pharmacology; D017482:Receptors, Thromboxane / Q000037:antagonists & inhibitors*; D013928:Thromboxane A2 / Q000037:antagonists & inhibitors / Q000378:metabolism*; D013930:Thromboxane-A Synthase / Q000037:antagonists & inhibitors*
D001562:Benzimidazoles; D001584:Benzoxepins; D008689:Methacrylates; D017482:Receptors, Thromboxane; D013928:Thromboxane A2; D011464:Epoprostenol; D013930:Thromboxane-A Synthase; C034364:ozagrel; D001241:Aspirin; C065729:KW 3635