Emerging drugs for preeclampsia – the endothelium as a target

Abstract

Preeclampsia, the development of new onset hypertension and proteinuria during pregnancy, affects ∼ 3 – 8% of all pregnancies and is a leading cause of maternal and perinatal morbidity and mortality. Despite the potentially devastating effects of this disease on the mother and the baby and the recent advances in understanding some of the pathological mechanisms responsible for the progression of preeclampsia, there are still few therapies available to manage the disease. The maternal syndrome of preeclampsia is characterized by systemic endothelial dysfunction; therefore, agents that improve endothelial function may hold promise to alleviate the symptoms of preeclampsia, delay the necessity for preterm delivery and improve neonatal outcomes. This brief review will focus on two therapies that are already approved for use in the US for other indications: PDE-5 inhibition to preserve nitric oxide – cGMP signaling to promote vasodilation and inhibition of the endothelin type A receptor to reduce vascular contraction.

Keywords:

• endothelin-1
• hypertension
• PDE-5
• pregnancy
• sildenafil

Declaration of interest

The authors are supported by grants from the American Heart Association (14SDG20160020 to SR Murphy) and the National Institutes of Health (K01DK095018 and P20GM104357 to JM Sasser and P01HL051971 and R01HL108618 to JP Granger). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.