Interactions of Thromboxane A2 Analogs and Prostaglandins in Isolated Dog Arteries

Abstract

Interactions of ONO3708, a thromboxane (TX) A2 analog, and epithiomethano-TXA2 (sTXA2) or prostaglandins (PGs) were investigated in helical strips of dog cerebral, coronary, renal, and mesenteric arteries. In these arterial strips sTXA2 (10-10 to 10-7 M) produced a dose-dependent contraction, whereas ONO3708 up to 10-6 M failed to contract the arteries but antagonized the contractile response to sTXA2. The inhibition tended to be greater in renal arteries than in the other arteries. Contractions induced by PGF2.alpha., PGE2, and PGD2 were also suppressed by treatment with low concentrations (3 .times. 10-9 and 10-8 M) of ONO3708. The attenuations of the response to sTXA2, PGF2.alpha., PGE2, and PGD2 did not appreciably differ. Norepinephrine-induced contractions were not influenced by ONO3708 up to 2 .times. 10-7 M. On the other hand, relaxant responses to PGI2 of cerebral and renal arteries were not reduced by ONO3708. Prostaglandin H2 produced a transient contraction followed by relaxation in cerebral and renal arteries. The contractile response was abolished by 10-7 M ONO3708, and that relaxation was potentiated. It may be concluded that ONO3708 selectively antagonizes the vasoconstrictor action of TXA2, its analogs, and PGs but does not alter the action of vasodilator PGs. At least in part, sTXA2, PGF2.alpha., PGE2, and PGD2 appear to share the same receptive site responsible for vascular contraction.