Thromboxane-mimetic U46619 causes depressor responses in anaesthetized rats.

Intravenous (i.v.) or intra-arterial injections of U46619, a thromboxane A2 (TxA2)-mimetic agent, into chloralose-anaesthetized rats dose-dependently decreased the arterial blood pressure. Indomethacin (8 mg kg-1) or atropine (1 mg kg-1), given i.v. 30 min beforehand, attenuated the hypotensive effect of U46619 i.v. whereas methysergide pretreatment (5 mg kg-1 i.v.) was without action. Pretreatment with AH23848 (5 mg kg-1 i.v.), a specific TxA2-receptor antagonist, completely abolished the depressor responses to U46619. The findings suggest that the vasodepressor effect of U46619 appears to be mediated via TxA2-receptor activation, with the release of prostacyclin and/or acetylcholine both of which produce vasodilatation.