title: 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.
authors.affiliation: a 1 University of Mississippi Medical Center, Department of Pharmacology and Toxicology , 2500 North State Street, Jackson, MS 39216, USA +1 601 984 1629 ; +1 601 984 1637 ; jsasser@umc.edu.
authors.forename: Jennifer M
authors.initials: JM
authors.lastname: Sasser
authors.affiliation: a 1 University of Mississippi Medical Center, Department of Pharmacology and Toxicology , 2500 North State Street, Jackson, MS 39216, USA +1 601 984 1629 ; +1 601 984 1637 ; jsasser@umc.edu.
authors.forename: Sydney R
authors.initials: SR
authors.lastname: Murphy
authors.affiliation: b 2 University of Mississippi Medical Center, Department of Physiology and Biophysics , 2500 North State Street, Jackson, MS 39216, USA.
authors.forename: Joey P
authors.initials: JP
authors.lastname: Granger
mesh_terms: D000818:Animals; D018450:Disease Progression; D015195:Drug Design; D065130:Endothelin A Receptor Antagonists / Q000494:pharmacology; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000473:pathology; D005260:Female; D006801:Humans; D007231:Infant, Newborn; D009569:Nitric Oxide / Q000378:metabolism; D058986:Phosphodiesterase 5 Inhibitors / Q000494:pharmacology; D011225:Pre-Eclampsia / Q000188:drug therapy* / Q000453:epidemiology / Q000503:physiopathology; D011247:Pregnancy; D011256:Pregnancy Outcome; D047928:Premature Birth / Q000209:etiology; D014664:Vasodilation / Q000187:drug effects
chemical_list: D065130:Endothelin A Receptor Antagonists; D058986:Phosphodiesterase 5 Inhibitors; D009569:Nitric Oxide
keywords: PDE-5; endothelin-1; hypertension; pregnancy; sildenafil