In-vitro study of the effect of anti-hypertensive drugs on placental hormones and angiogenic proteins synthesis in pre-eclampsia

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Gangooly, Subrata
Muttukrishna, Shanthi
Jauniaux, Eric
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Introduction: 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, a-methyldopa and pravastatin on the synthesis of placental hormonal and angiogenic proteins know to be altered in PE. Design: Placental villous explants from late onset PE (n = 3) and normotensive controls (n = 6) were cultured for 3 days at 10 and 20% oxygen (O-2) 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 dependant 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 O-2 concentration cultures, except for Activin, A which was significantly (p<0.05) higher in controls at 10% O-2. Interpretation: 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.
Human early pregnancy , Tyrosine kinase 1 , Oxidative stress , Activin A , Hypertensive disorders , Soluble endoglin , Blood flow , Inhibin , Agents , Oxygen
Gangooly S, Muttukrishna S, Jauniaux E (2014) In-Vitro Study of the Effect of Anti-Hypertensive Drugs on Placental Hormones and Angiogenic Proteins Synthesis in Pre-Eclampsia. PLoS ONE 9(9): e107644. doi:10.1371/journal.pone.0107644