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Excessive placental secretion of neurokinin B during the third trimester causes pre-eclampsia

Nature volume 405, pages 797–800 (2000)Cite this article

Abstract

Pre-eclampsia is a principal cause of maternal morbidity and mortality, affecting 5–10% of first pregnancies worldwide. Manifestations include increased blood pressure, proteinuria, coagulopathy and peripheral and cerebral oedema. Although the aetiology and pathogenesis remain to be elucidated, the placenta is undoubtedly involved, as termination of pregnancy eradicates the disease. Here we have cloned a complementary DNA from human placental messenger RNA encoding a precursor protein of 121 amino acids which gives rise to a mature peptide identical to the neuropeptide neurokinin B (NKB)1 of other mammalian species. In female rats, concentrations of NKB several-fold above that of an animal 20 days into pregnancy caused substantial pressor activity. In human pregnancy, the expression of NKB was confined to the outer syncytiotrophoblast of the placenta, significant concentrations of NKB could be detected in plasma as early as week 9, and plasma concentrations of NKB were grossly elevated in pregnancy-induced hypertension and pre-eclampsia. We conclude that elevated levels of NKB in early pregnancy may be an indicator of hypertension and pre-eclampsia, and that treatment with certain neurokinin receptor antagonists may be useful in alleviating the symptoms.

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Figure 1: Localization of neurokinin B mRNA expression in vertical sections of the placenta.
Figure 2: Neurokinin B levels in the plasma of 30 normotensive women (filled circles) were determined in samples taken throughout pregnancy and at term in 16 different women (open circles).
Figure 3: Changes in heart rate and blood pressure during infusion of saline (open circles, n = 3) or incremental doses of NKB (filled circles, n = 6) in conscious unrestrained female rats.

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Acknowledgements

This work was supported by the Medical Research Council.

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Authors and Affiliations

  1. School of Animal and Microbial Sciences, The University of Reading, Reading, RG6 6AJ, UK

    N. M. Page, R. J. Woods, K. Lomthaisong, R. T. Gladwell, D. J. Butlin & P. J. Lowry

  2. School of Biomedical Sciences, The University of Nottingham, Nottingham, NG7 2UH, UK

    S. M. Gardiner

  3. Department of Obstetrics and Gynaecology St George's Hospital, London, SW17 0QT, UK

    I. T. Manyonda

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  1. N. M. Page
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Page, N., Woods, R., Gardiner, S. et al. Excessive placental secretion of neurokinin B during the third trimester causes pre-eclampsia. Nature 405, 797–800 (2000). https://doi.org/10.1038/35015579

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