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Effects of Oxygen Tension and Normalization Pressure on Endothelin-lnduced Constriction of Human Placental Chorionic Plate Arteries

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Abstract

Objectives

eitFetoplacental blood vessels constrict in response to endothelin (ET-1) or reduced oxygen tension in the placental cotyledon perfused in vitro. In nonplacental resistance arteries, hypoxia and ET-1 induce constriction by promoting Ca influx into smooth muscle through membrane ion channels, which include voltage-gated Ca channels (VGCCs). We hypothesized that VGCCs are involved in ET-1— induced constriction of fetoplacental resistance vessels and that their contribution to constriction is enhanced at low oxygen tension.

Methods

eitChorionic plate small arteries from term placentas were studied using parallel wire myography. Arteries were normalized at 0.9 of L5.1 kPa (“low stretch” —25 mm Hg; approximating physiologic vascular pressure) or 0.9 of L133 kPa (“high stretch” — 42 mm Hg) and experiments performed at oxygen tensions of 156, 38, and 15 mm Hg.

Results

When chorionic plate arteries were normalized at low stretch, oxygen tension did not affect constriction to ET-1. Nifedipine (10 M), a blocker of L-type VGCCs, inhibited ET-1 (EC80eit)-induced constriction to a similar extent at each oxygen tension (52% to 64% inhibition). In contrast, when arteries were normalized at high stretch, constriction to ET-1 was greater at 38 than at 156 or 15 mm Hg oxygen and nifedipine inhibition of ET-1—induced constriction was greater at 38 and 15 mm Hg than at 156 mm Hg oxygen.

Conclusions

eitVGCCS and nifedipine-insensitive processes underlie the contractile response of chorionic plate arteries to ET-1 and their relative contribution to vasoconstriction is modulated by oxygen tension when vessels are normalized at high stretch. However, contrary to our hypothesis, the response of chorionic plate arteries to ET-1 is not modulated by oxygen when vessels are normalized at physiologic pressure.

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Authors and Affiliations

  1. Academic Unit of Child Health, Division of Human Development, St Mary’s Hospital, The Medical School, University of Manchester, Hathersage Road, Manchester, M13 OJH, UK

    Emma J. Cooper BSc, Mark Wareing PhD, Susan L. Greenwood PhD & Philip N. Baker MBS, DM

Authors
  1. Emma J. Cooper BSc
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  2. Mark Wareing PhD
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  3. Susan L. Greenwood PhD
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  4. Philip N. Baker MBS, DM
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Corresponding author

Correspondence to Susan L. Greenwood PhD.

Additional information

From the Maternal and Fetal Health Research Centre, St Mary’s Hospital, The Medical School, University of Manchester, Manchester, UK.

Supported by Tommy’s: the baby charity.

The authors are grateful to the midwives of the Central Delivery Unit at St Mary’s Hospital for their help in obtaining patient consent.

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Cooper, E.J., Wareing, M., Greenwood, S.L. et al. Effects of Oxygen Tension and Normalization Pressure on Endothelin-lnduced Constriction of Human Placental Chorionic Plate Arteries. Reprod. Sci. 12, 488–494 (2005). https://doi.org/10.1016/j.jsgi.2005.05.004

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  • DOI: https://doi.org/10.1016/j.jsgi.2005.05.004

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