Adriamycin-Related Hypertension in Pregnant Rats: Response to a Thromboxane Receptor Antagonist

1. In previous works we have described the development of hypertension and aggravation of proteinuria in rats who became pregnant after the administration of Adriamycin. This was associated with an increase in the glomerular thromboxane B₂—prostaglandin E₂ ratio.

2. To assess the pathogenetic role of thromboxane in this model, female Wistar rats were mated 2 weeks after receiving Adriamycin (3.5 mg/kg intravenously). Rats were then treated with the thromboxane-receptor antagonist daltroban, 60 mg day⁻¹ kg⁻¹ orally, beginning on day 11 of pregnancy. Systolic blood pressure, proteinuria and the urinary excretion of thromboxane B₂, 6-keto-prostaglandin F_1α and prostaglandin E₂ were measured serially before mating, and on days 14 and 21 of pregnancy. The results were compared with those in Adriamycin-(treated) pregnant rats not treated with daltroban, Adriamycin-treated virgin rats and normal virgin or pregnant rats either treated or untreated with daltroban.

3. In daltroban-treated pregnant and virgin rats treated with Adriamycin, systolic blood pressure remained normal, whereas it increased significantly (P < 0.05) in untreated animals. On day 14, blood pressure was higher in non-daltroban-treated Adriamycin-treated pregnant rats than in non-daltroban-treated Adriamycin-treated virgin rats. Treatment had no effect on blood pressure in normal virgin or pregnant rats. Proteinuria was higher in pregnant rats treated with Adriamycin than in Adriamycin-treated virgin rats, but it was not reduced by daltroban. Urinary thromboxane B₂ tended to increase in Adriamycin-treated virgin rats and was significantly higher than in the other groups at the period corresponding to end-pregnancy, whereas in Adriamycin-treated pregnant rats thromboxane B₂ was not significantly increased. Daltroban did not change the urinary excretion of thromboxane B₂, whereas urinary 6-keto-prostaglandin F_1α increased significantly.

4. We conclude that elevation of blood pressure after Adriamycin in rats is mediated by thromboxane B₂/endoperoxide receptors. This suggests a further analogy, in this model, with one of the pathogenetic mechanisms of pregnancy-related hypertension.