Actions of a novel thromboxane A2-receptor antagonist, S-145, on isolated monkey and cat arteries

The effects of a novel thromboxane (Tx) A2-receptor antagonist, S-145, were investigated mainly in helical strips of monkey and cat arteries. S-145 (3 x 10(-10) to 3 x 10(-9) M) attenuated the contraction induced by U46619 (2 x 10(-10) to 10(-7) M), which produced concentration-dependent contraction in monkey cerebral, coronary, and mesenteric arteries, and cat cerebral arteries. The attenuation in the different monkey arteries did not differ much, and it tended to be greater in cat cerebral arteries than in monkey at concentrations of less than 10(-9) M S-145. S-145 also suppressed contractions in cat cerebral arteries induced by prostaglandin (PG) F2 alpha, PGE2, and PGD2. However, S-145 did not affect the contractile responses to PGF2 alpha in cat iris sphincter muscle and to PGE2 in guinea pig ileum. In cat mesenteric arteries, S-145 did not affect contractions induced by norepinephrine or K+, or relaxations induced by PGI2 or adenosine. The addition of S-145 (10(-9)-10(-8) M) produced a transient contraction in cat cerebral arteries, and when S-145 (3 x 10(-11) to 3 x 10(-7) M) was cumulatively added, the contraction was not produced. The measurement of antagonistic potency of S-145 was not complicated by its agonistic effect, since the former potency was always determined after confirming absence of the latter effect. These results suggest that S-145 is a potent TxA2-receptor antagonist with partial agonistic activity in vascular smooth muscle. PGF2 alpha, PGE2, and PGD2, however, at least in part, seemed to interact with the TxA2 receptor in vascular smooth muscle.