Sildenafil for the treatment of preeclampsia, an update: should we still be enthusiastic?

ABSTRACT

Preeclampsia is a hypertensive disorder of pregnancy and the clinical manifestation of severe endothelial dysfunction associated with maternal and foetal morbidity and mortality. The primum movens of the disease is the defect of invasion of the uterine arteries by foetal syncytiotrophoblasts, which causes a maladaptive placental response to chronic hypoxia and the secretion of the soluble form of type 1 vascular growth endothelial factor receptor, also called soluble fms-like tyrosine kinase 1 (sFlt-1), the major player in the pathophysiology of the disease. Among its different effects, sFlt-1 induces abnormal sensitivity of the maternal vessels to the vasoconstrictor angiotensin II. This leads to the hypertensive phenotype, recently shown to be abrogated by the administration of sildenafil citrate, which can potentiate the vasodilatory mediator nitrite oxide. This review focuses on the mechanisms of maternal endothelial dysfunction in preeclampsia and discusses the therapeutic window of sildenafil use in the context of preeclampsia, based on the results from preclinical studies and clinical trials. Safety issues recently reported in neonates have considerably narrowed this window.