The effect of pregnancy on the response to the TxA2/PGH2 analogue U- 46619 in rabbits

G. Losonczy, I. Mucha, J. DiPirro, J. Sweeney, G. Brown, J. Brentjens, R. Venuto

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We compared the hemodynamic actions of U-46619, a stable thromboxane A2 (TxA2) prostaglandin H2 (PGH2) analogue, in nonpregnant (NP) rabbits with those observed in late pregnant (P) rabbits. An intravenous injection of U- 46619 (10 μg) to each of eight NP chronically instrumented rabbits (mean body weight 3.4 kg) induced an immediate (1 min) and reversible 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 intravenous injection of the drug (10 μg), while CO remained unchanged. The fall of CO in NP rabbits was associated with the temporary disappearance 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 aortic blood, whereas caval platelet counts were unchanged until 90 s (-6%, P < 0.05). In contrast, intraaortic administration of this drug (10 μg) to NP rabbits resulted in neither thrombocytopenia nor hypotension. U-46619 (10-30 μg 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 receptors. The data indicate that U-46619 induces a fall of arterial pressure simultaneous with intravascular platelet aggregation. A relationship between the refractoriness of P rabbits to the hypotensive action of intravenous U- 46619 and the diminished aggregatory response of isolated platelets of P rabbits to this TxA2/PGH2 agonist is suggested.

Original languageEnglish
Pages (from-to)R772-R780
JournalAmerican Journal of Physiology - Regulatory Integrative and Comparative Physiology
Issue number4 34-4
Publication statusPublished - Jan 1 1993



  • arterial pressure
  • platelet aggregation
  • pregnancy
  • rabbits
  • thromboxane

ASJC Scopus subject areas

  • Physiology
  • Physiology (medical)

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