4.6 Article

The L-NAME mouse model of preeclampsia and impact to long-term maternal cardiovascular health

Journal

LIFE SCIENCE ALLIANCE
Volume 5, Issue 12, Pages -

Publisher

LIFE SCIENCE ALLIANCE LLC
DOI: 10.26508/lsa.202201517

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Funding

  1. Trevor B Kilvington Bequest
  2. National Health and Medical Research Council [1146128]

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Preeclampsia affects 2-8% of pregnancies worldwide. This study evaluates the effect of L-NAME in modeling preeclampsia in mice and its long-term effects on maternal cardiovascular health. The results show that L-NAME administration mimics key characteristics of preeclampsia but does not model the increased cardiovascular disease risk seen after preeclampsia.
Preeclampsia affects similar to 2-8% of pregnancies worldwide. It is associated with increased long-term maternal cardiovascular disease risk. This study assesses the effect of the vasoconstrictor N(omega)-nitro-L-arginine methyl ester (L-NAME) in modelling preeclampsia in mice, and its long-term effects on maternal cardiovascular health. In this study, we found that L-NAME administration mimicked key characteristics of preeclampsia, including elevated blood pressure, impaired fetal and placental growth, and increased circulating endothelin-1 (vasoconstrictor), soluble fms-like tyrosine kinase-1 (anti-angiogenic factor), and C-reactive protein (inflammatory marker). Post-delivery, mice that received L-NAME in pregnancy recovered, with no discernible changes in measured cardiovascular indices at 1-, 2-, and 4-wk post-delivery, compared with matched controls. At 10-wk post-delivery, arteries collected from the L-NAME mice constricted significantly more to phenylephrine than controls. In addition, these mice had increased kidney Mmp9:Timp1 and heart Tnf mRNA expression, indicating increased inflammation. These findings suggest that though administration of L-NAME in mice certainly models key characteristics of pre-eclampsia during pregnancy, it does not appear to model the adverse increase in cardiovascular disease risk seen in individuals after preeclampsia.

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