THE HYPOTENSIVE ACTION OF ENDOPEROXIDE ANALOGS IN THE RAT

The endoperoxide analogues U46619 and U44069 when injected intravenous ly (i.v.), into the femoral artery or directly into the aortic arch in chloralose-anaesthetised rats, decreased arterial blood pressure dose -dependently. Treatment i.v. 30 min beforehand with indomethacin (8-15 mg/kg) or atropine (2 mg/kg) attenuated the hypotensive effect of U46 619 or U44069, but methysergide (5 mg/kg) was ineffective. Combined pr etreatment with indomethacin and atropine reduced further the hypotens ive action of the endoperoxide analogues, but was unable to block the effect completely. However, pretreatment i.v. with AH23848, a specific thromboxane A2 (TXA2)-receptor antagonist, completely abolished the d epressor responses to U46619 and U44069. Bilateral vagotomy did not ch ange the hypotensive effect of both endoperoxide analogues. These find ings suggest that the vasodepressor action of U46619 or U44069 is not a reflex mechanism, nor is it related to 5-hydroxytryptamine release. This effect appears to be mediated via TXA2-receptor stimulation, with the liberation of prostacyclin and/or acetylcholine or possibly an en dothelium-derived relaxing factor (EDRF), all of which produce vasodil atation.