title: Effect of antihypertensive therapy with alpha methyldopa on levels of angiogenic factors in pregnancies with hypertensive disorders.
abstract: BACKGROUND
  Antihypertensive drugs are believed to lower blood pressure in pre-eclampsia by direct or central vasodilatory mechanisms. However, they could also act by decreasing production of anti-angiogenic proteins involved in the pathophysiology of hypertension and proteinuria in pre-eclampsia (PE). The aim of our study was to evaluate the impact of antihypertensive therapy with alpha methyldopa on maternal circulating levels and placental production of soluble fms-like tyrosine kinase 1 (sFlt-1), soluble endoglin (sEng), vascular endothelial growth factor (VEGF) and placental growth factor (PlGF) in hypertensive disorders of pregnancy.
  
  
  RESULTS
  In a study conducted at University College Hospital and the Homerton University Hospital in London, we recruited 51 women with PE, 29 with gestational hypertension (GH), and 80 matched normotensive controls. Eight (16%) of the women with PE had severe disease. Placental samples were obtained from a further 48 women (14 PE, 10 GH and 24 matched controls). Serum levels of angiogenic factors were measured before and 24-48 hours after commencing antihypertensive therapy with alpha methyldopa for clinical indications. The same parameters were measured in placental extracts. In both PE (P<0.0001) and GH (P<0.05), serum sFlt-1 was increased and PlGF reduced at all gestations (P<0.001) compared to controls. Serum sEng levels were also increased in PE. Placental concentration of sFlt-1 and sEng was significantly higher in women with PE compared to controls and women with GH (P<0.0001). The concentration of PlGF was significantly lower in the placental tissue of women with PE compared to GH (P = 0.008). Antihypertensive treatment was associated with a significant fall in serum and placental content of sFlt1 and sEng in PE only.
  
  
  CONCLUSIONS
  Our data suggest that alpha methyldopa may have a specific effect on placental and/or endothelial cell function in pre-eclampsia patients, altering angiogenic proteins.
authors.affiliation: The Homerton University Hospital NHS Trust, Queen Mary and Westfield College, University of London, London, United Kingdom. asmakhalil79@googlemail.com
authors.forename: Asma
authors.initials: A
authors.lastname: Khalil
authors.forename: Shanthi
authors.initials: S
authors.lastname: Muttukrishna
authors.forename: Kevin
authors.initials: K
authors.lastname: Harrington
authors.forename: Eric
authors.initials: E
authors.lastname: Jauniaux
mesh_terms: D020533:Angiogenesis Inhibitors / Q000494:pharmacology*; D015703:Antigens, CD / Q000378:metabolism; D000959:Antihypertensive Agents / Q000494:pharmacology*; D000071063:Endoglin; D005260:Female; D006801:Humans; D006973:Hypertension / Q000150:complications / Q000188:drug therapy*; D008750:Methyldopa / Q000494:pharmacology*; D009389:Neovascularization, Pathologic; D000072483:Placenta Growth Factor; D011247:Pregnancy; D011249:Pregnancy Complications, Cardiovascular; D011257:Pregnancy Proteins / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000378:metabolism; D018608:Ultrasonography, Doppler / Q000379:methods; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism; D040281:Vascular Endothelial Growth Factor Receptor-1 / Q000378:metabolism
chemical_list: D020533:Angiogenesis Inhibitors; D015703:Antigens, CD; D000959:Antihypertensive Agents; C064206:ENG protein, human; D000071063:Endoglin; C000608036:PGF protein, human; D011257:Pregnancy Proteins; D011956:Receptors, Cell Surface; D042461:Vascular Endothelial Growth Factor A; D000072483:Placenta Growth Factor; D008750:Methyldopa; C501162:FLT1 protein, human; D040281:Vascular Endothelial Growth Factor Receptor-1