THE EFFECT OF PREGNANCY ON THE RESPONSE TO THE TXA(2) PGH(2) ANALOG U-46619 IN RABBITS/

We compared the hemodynamic actions of U-46619, a stable thromboxane A 2 (TxA2) prostaglandin H-2 (PGH2) analogue, in nonpregnant (NP) rabbit s with those observed in late pregnant (P) rabbits. An intravenous inj ection of U-46619 (10 mug) to each of eight NP chronically instrumente d rabbits (mean body weight 3.4 kg) induced an immediate (1 min) and r eversible fall of cardiac output (CO, 66%) and mean arterial pressure (MAP, 41%, both P < 0.01). P rabbits (n = 6, mean body weight 3.8 kg), however, responded with an elevation of MAP (5%, P < 0.02) upon intra venous injection of the drug (10 mug), while CO remained unchanged. Th e fall of CO in NP rabbits was associated with the temporary disappear ance of a fraction of circulating platelets between the superior vena cava and the aortic arch. The number of platelets at 30 and 60 s after U-46619 was reduced (P < 0.05) by 14 and 20% respectively in the aort ic blood, whereas caval platelet counts were unchanged until 90 s (-6% , P < 0.05). In contrast, intraaortic administration of this drug (10 mug) to NP rabbits resulted in neither thrombocytopenia nor hypotensio n. U-46619 (10-30 mug iv) caused no decrease in platelet count in the aorta of P rabbits. In vitro, U-46619-induced aggregation of platelets harvested from P rabbits was also blunted (P < 0.001). This could not be attributed to reduced affinity or number of platelet thromboxane r eceptors. The data indicate that U-46619 induces a fall of arterial pr essure simultaneous with intravascular platelet aggregation. A relatio nship between the refractoriness of P rabbits to the hypotensive actio n of intravenous U-46619 and the diminished aggregatory response of is olated platelets of P rabbits to this TxA2/PGH2, agonist is suggested.