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Maternal anti-hypertensive medicines & placental vascular function


Project Description

A range of anti-hypertensive medicines are prescribed to women with chronic hypertension in pregnancy, that enter the fetal circulation. Current practice is to select from a number of medications which are considered safe in pregnancy, including Ca2+-channel inhibitors and α/β-(adrenergic) receptor blockers. There is no clear evidence to guide clinicians or women on the choice of agent as the safest option for fetal outcome. The effect of anti-hypertensive medicines on fetoplacental vasculature and its function is not known, with respect to its structural development, the regulation of vascular tone and oxygen transfer. Cohorts of women who have and have not received anti-hypertensive medicines during pregnancy will be followed through into a variety of laboratory investigations. For the first time, the vasoactive effects of anti-hypertensive drugs on the fetoplacental circulation will be assessed in this study using several approaches. Firstly, you will use ex vivo dual human placental perfusion and human chorionic plate artery wire myography to assess resistance to fetal blood flow. Also, using placental endothelial cell models, you will investigate the relative effects of different pregnancy-prescribed antihypertensive medications on fetoplacental: endothelial nitric oxide signalling, metabolism and survival; branching angiogenesis and related endocrinology. Furthermore, you will study the effects of drugs on placental microvasculature density and wall-structure. This information will provide a badly needed evidence base to allow obstetricians to prescribe the safest and most effective medications for women with hypertensive pregnancy disorders, relating to the health and development of their baby.

Entry Requirements:
Candidates are expected to hold (or be about to obtain) a minimum upper second class honours degree (or equivalent) in a related area / subject. Qualified medical student specialising in obstetric medicine are particularly encouraged to apply.

For information on how to apply for this project, please visit the Faculty of Biology, Medicine and Health Doctoral Academy website (https://www.bmh.manchester.ac.uk/study/research/apply/). Informal enquiries may be made directly to the primary supervisor.

For international students we also offer a unique 4 year PhD programme that gives you the opportunity to undertake an accredited Teaching Certificate whilst carrying out an independent research project across a range of biological, medical and health sciences. For more information please visit http://www.internationalphd.manchester.ac.uk

Funding Notes

This project has a Band 2 fee. Details of our different fee bands can be found on our website (View Website). For information on how to apply for this project, please visit the Faculty of Biology, Medicine and Health Doctoral Academy website (View Website).

Informal enquiries may be made directly to the primary supervisor.

References

Cea Soriano, L., Bateman, B. T., Garcia Rodriguez, L. A. & Hernandez-Diaz, S. Prescription of antihypertensive medications during pregnancy in the UK. Pharmacoepidemiol Drug Saf 23, 1051-1058, doi:10.1002/pds.3641 (2014).

von Dadelszen, P. et al. Fall in mean arterial pressure and fetal growth restriction in pregnancy hypertension: a meta-analysis. Lancet 355, 87-92 (2000).

Webster, L. M. et al. Labetalol Versus Nifedipine as Antihypertensive Treatment for Chronic Hypertension in Pregnancy: A Randomized Controlled Trial. Hypertension 70, 915-922,

Krause, B. J., Hanson, M. A. & Casanello, P. Role of nitric oxide in placental vascular development and function. Placenta 32, 797-805, doi:10.1016/j.placenta.2011.06.025 (2011).

Khalil, A., Muttukrishna, S., Harrington, K. & Jauniaux, E. Effect of antihypertensive therapy with alpha methyldopa on levels of angiogenic factors in pregnancies with hypertensive disorders. PLoS One 3, e2766, doi:10.1371/journal.pone.0002766 (2008).

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