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Effect of antihypertensive therapy with alpha methyldopa on levels of angiogenic factors in pregnancies with hypertensive disorders.

Khalil, A; Muttukrishna, S; Harrington, K; Jauniaux, E (2008) Effect of antihypertensive therapy with alpha methyldopa on levels of angiogenic factors in pregnancies with hypertensive disorders. PLoS One, 3 (7). e2766 (1)-e2766 (8). ISSN 1932-6203 https://doi.org/10.1371/journal.pone.0002766
SGUL Authors: Khalil, Asma

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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. Methodology/Principal Findings: 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.

Item Type: Article
Additional Information: Copyright: 2008 Khalil et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Keywords: Angiogenesis Inhibitors, Antigens, CD, Antihypertensive Agents, Female, Humans, Hypertension, Methyldopa, Neovascularization, Pathologic, Pregnancy, Pregnancy Complications, Cardiovascular, Pregnancy Proteins, Receptors, Cell Surface, Ultrasonography, Doppler, Vascular Endothelial Growth Factor A, Vascular Endothelial Growth Factor Receptor-1, General Science & Technology, MD Multidisciplinary
SGUL Research Institute / Research Centre: Academic Structure > Molecular and Clinical Sciences Research Institute (MCS)
Academic Structure > Molecular and Clinical Sciences Research Institute (MCS) > Vascular (INCCVA)
Journal or Publication Title: PLoS One
ISSN: 1932-6203
Related URLs:
Dates:
DateEvent
23 July 2008Published
PubMed ID: 18648513
Web of Science ID: 18648513
Go to PubMed abstract
URI: https://openaccess.sgul.ac.uk/id/eprint/107071
Publisher's version: https://doi.org/10.1371/journal.pone.0002766

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