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

Abstract

ABSTRACT-We examined the effects of KW-3635, a thromboxane (TX) A2-receptor antagonist, and OKY-046, a TX synthetase inhibitor, on the prostaglandin (PG) 12 production in endothelium-intact and -in jured 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 an tagonist and the TX synthetase inhibitor have some advantages over aspirin when used for the prevention of acute thrombosis after percutaneous transluminal angioplasty.

Enhancement of activated β1-integrin expression by prostaglandin E2 via EP receptors in isolated human coronary arterial endothelial cells: implication for the treatment of Kawasaki disease

“…Endogenous PGD 2 decreases vascular cell adhesion molecule-1 (VCAM-1) expression and VCAM-1 mRNA expression in human umbilical vein endothelial cells [34]. Clinical doses of aspirin for acute KD (30-50 mg/kg/ day) are able to sufficiently inhibit production of PGI 2 and PGD 2 [37,38]. Regarding the PG cascade, it is unlikely that aspirin is an adequate treatment for acute KD because PGI 2 and PGD 2 could act to attenuate vasculitis, and impairment of their production by aspirin would be disadvantageous.…”