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Effect of Gestational Diabetes on Maternal Artery Function

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Abstract

Endothelial dysfunction has been observed systemically in women with gestational diabetes (GDM). Important cardiovascular adaptations occur during pregnancy, including enhanced endothelium-dependent vasodilation in systemic and uterine arteries, which are necessary to ensure the health of both mother and fetus. The effects of GDM, however, on uterine artery function and the possible mechanisms that mediate endothelial dysfunction remain unknown. The aim of this study was to utilize a mouse model of GDM to investigate (a) effects on uteroplacental flow, (b) endothelial function of uterine and mesenteric arteries, and (c) possible mechanisms of any dysfunction observed. Pregnant mice heterozygous for a leptin receptor mutation (Leprdb/+; He) spontaneously develop GDM and were compared to wild-type (WT) mice at day 18.5 of gestation. Uterine artery flow was assessed using ultrasound biomicroscopy. Uterine and mesenteric artery function was assessed using wire myography. Arterial superoxide production was measured using oxidative fluorescence microphotography. In vivo uteroplacental perfusion was impaired in mice with GDM, indicated by a significant increase in uterine artery resistance index. Maximal endothelium-dependent relaxation to methacholine was significantly impaired in mesenteric arteries from mice with GDM, while sensitivity was significantly reduced in uterine arteries. Both uterine and mesenteric arteries from mice with GDM exhibited a greater dependence on nitric oxide and increased superoxide production compared with those from mice with a healthy pregnancy. A significant source of superoxide in GDM mice was uncoupled nitric oxide synthase. These changes may contribute to the development of some of the fetal and maternal complication associated with GDM.

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Authors and Affiliations

  1. Department of Obstetrics and Gynecology/Physiology, 220 HMRC, University of Alberta, Edmonton, AB, Canada, T6G 2S2

    J. L. Stanley PhD, C. C. Cheung BSc, C. F. Rueda-Clausen MD, S. Sankaralingam PhD, P. N. Baker DM & Sandra T. Davidge PhD

  2. Maternal & Fetal Health Research Group, University of Manchester, St Mary’s Hospital, Oxford Road, Manchester, UK

    J. L. Stanley PhD & P. N. Baker DM

  3. Cardiovascular Research Centre, University of Alberta, Edmonton, Alberta, Canada

    J. L. Stanley PhD, C. F. Rueda-Clausen MD, P. N. Baker DM & Sandra T. Davidge PhD

  4. Womens and Children’s Health Research Centre, Edmonton, Alberta, Canada

    J. L. Stanley PhD, C. F. Rueda-Clausen MD, P. N. Baker DM & Sandra T. Davidge PhD

  5. Mazankowski Alberta Heart Institute, Edmonton, Alberta, Canada

    J. L. Stanley PhD, C. F. Rueda-Clausen MD, P. N. Baker DM & Sandra T. Davidge PhD

Authors
  1. J. L. Stanley PhD
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  2. C. C. Cheung BSc
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  3. C. F. Rueda-Clausen MD
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  4. S. Sankaralingam PhD
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  5. P. N. Baker DM
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  6. Sandra T. Davidge PhD
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Correspondence to Sandra T. Davidge PhD.

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Authors’ Note

SD is an AHFMR Scientist and a Canada Research Chair in Women’s Cardiovascular Health.

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Stanley, J.L., Cheung, C.C., Rueda-Clausen, C.F. et al. Effect of Gestational Diabetes on Maternal Artery Function. Reprod. Sci. 18, 342–352 (2011). https://doi.org/10.1177/1933719110393029

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