Mifepristone (RU 486) induces vasodilation and inhibits platelet aggregation: nongenomic and genomic action to cause hemorrhage.

摘要

BACKGROUND: The regimen mifepristone/misoprostol is an established and highly effective method for early termination of pregnancy. However, its side effects such as a significantly long bleeding time and hemorrhage have been scantly studied. STUDY DESIGN: Human umbilical artery (HUA) from pregnant women undergoing elective cesarean section at term and rat thoracic aorta (RTA) were isometrically recorded. The vasorelaxing effect of mifepristone was analyzed on the contractile responses induced by KCl or serotonin (5-HT); moreover, the potential response of mifepristone on adenosine diphosphate (ADP)-induced human platelet aggregation was also evaluated. RESULTS: This study describes that mifepristone elicits (1) rapid and reversible vasorelaxation on KCl- or 5-HT-induced contraction in HUA and RTA with and without endothelium and (2) immediate prevention of ADP-induced human platelet aggregation. CONCLUSIONS: These effects seem to be responsible for increased and prolonged hemorrhage. Since mifepristone-prevented platelet aggregation was observed in the anucleate platelets, and mifepristone-induced vasorelaxation remained unaffected in de-endothelized tissues, by inhibitors of transcription and translation and a nitric oxide (NO) synthase inhibitor, a nongenomic endothelium- and NO-independent mechanism was revealed. Additionally, the results indicated a blockade of voltage- and receptor-operated calcium channels. The antiglucocorticoid genomic action of mifepristone, by inducing an excess of NO, may also contribute to exacerbated hemorrhage.