title: In-vitro study of the effect of anti-hypertensive drugs on placental hormones and angiogenic proteins synthesis in pre-eclampsia.
abstract: BACKGROUND
  Antihypertensive drugs lower the maternal blood pressure in pre-eclampsia (PE) by direct or central vasodilatory mechanisms but little is known about the direct effects of these drugs on placental functions.
  
  
  OBJECTIVE
  The aim of our study is to evaluate the effect of labetolol, hydralazine, α-methyldopa and pravastatin on the synthesis of placental hormonal and angiogenic proteins know to be altered in PE.
  
  
  METHODS
  Placental villous explants from late onset PE (n = 3) and normotensive controls (n = 6) were cultured for 3 days at 10 and 20% oxygen (O2) with variable doses anti-hypertensive drugs. The levels of activin A, inhibin A, human Chorionic Gonadotrophin (hCG), soluble fms-like tyrosine kinase-1 (sFlt-1) and soluble endoglin (sEng) were measured in explant culture media on day 1, 2 and 3 using standard immunoassays. Data at day 1 and day 3 were compared.
  
  
  RESULTS
  Spontaneous secretion of sEndoglin and sFlt-1 were higher (p < 0.05) in villous explants from PE pregnancies compared to controls. There was a significant time dependent decrease in the secretion of sFlt-1 and sEndoglin in PE cases, which was seen only for sFlt-1 in controls. In both PE cases and controls the placental protein secretions were not affected by varying doses of anti-hypertensive drugs or the different O2 concentration cultures, except for Activin, A which was significantly (p < 0.05) higher in controls at 10% O2.
  
  
  CONCLUSIONS
  Our findings suggest that the changes previously observed in maternal serum hormones and angiogenic proteins level after anti-hypertensive treatment in PE could be due to a systemic effect of the drugs on maternal blood pressure and circulation rather than a direct effect of these drugs on placental biosynthesis and/or secretion.
authors.affiliation: Institute for Women's Health, University College London, London, United Kingdom.
authors.forename: Subrata
authors.initials: S
authors.lastname: Gangooly
authors.affiliation: Institute for Women's Health, University College London, London, United Kingdom; Anu Research Centre, Department of Obstetrics and Gynaecology, University College Cork, Cork University Maternity Hospital, Cork, Republic of Ireland.
authors.forename: Shanthi
authors.initials: S
authors.lastname: Muttukrishna
authors.affiliation: Institute for Women's Health, University College London, London, United Kingdom.
authors.forename: Eric
authors.initials: E
authors.lastname: Jauniaux
mesh_terms: D028341:Activins / Q000378:metabolism; D042501:Angiogenic Proteins / Q000378:metabolism*; D015703:Antigens, CD / Q000378:metabolism; D000959:Antihypertensive Agents / Q000494:pharmacology*; D006063:Chorionic Gonadotropin / Q000378:metabolism; D002824:Chorionic Villi / Q000187:drug effects / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D000071063:Endoglin; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D006830:Hydralazine / Q000494:pharmacology; D007741:Labetalol / Q000494:pharmacology; D008750:Methyldopa / Q000494:pharmacology; D010920:Placenta / Q000187:drug effects* / Q000378:metabolism; D010926:Placental Hormones / Q000378:metabolism*; D017035:Pravastatin / Q000494:pharmacology; D011225:Pre-Eclampsia / Q000188:drug therapy / Q000378:metabolism; D011247:Pregnancy; D011956:Receptors, Cell Surface / Q000378:metabolism; D013997:Time Factors; D046509:Tissue Culture Techniques; D040281:Vascular Endothelial Growth Factor Receptor-1 / Q000378:metabolism
chemical_list: D042501:Angiogenic Proteins; D015703:Antigens, CD; D000959:Antihypertensive Agents; D006063:Chorionic Gonadotropin; C064206:ENG protein, human; D000071063:Endoglin; D010926:Placental Hormones; D011956:Receptors, Cell Surface; C422405:activin A; D028341:Activins; D006830:Hydralazine; D008750:Methyldopa; C501162:FLT1 protein, human; D040281:Vascular Endothelial Growth Factor Receptor-1; D017035:Pravastatin; D007741:Labetalol