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

  • Life Sci Alliance. 2022 Aug 5;5(12):e202201517. doi: 10.26508/lsa.202201517.
Natasha de Alwis  1  2 ,  Natalie K Binder  3  2 ,  Sally Beard  3  2 ,  Yeukai Tm Mangwiro  3  2 ,  Elif Kadife  2  4 ,  James Sm Cuffe  5 ,  Emerson Keenan  2  4 ,  Bianca R Fato  3  2 ,  Tu'uhevaha J Kaitu'u-Lino  2  6 ,  Fiona C Brownfoot  2  4 ,  Sarah A Marshall  7 ,  Natalie J Hannan  3  2
Affiliations
  • 1. Department of Obstetrics and Gynaecology, Therapeutics Discovery and Vascular Function Group, The University of Melbourne and Mercy Hospital for Women, Heidelberg, Australia [email protected].
  • 2. Mercy Perinatal, Heidelberg, Australia.
  • 3. Department of Obstetrics and Gynaecology, Therapeutics Discovery and Vascular Function Group, The University of Melbourne and Mercy Hospital for Women, Heidelberg, Australia.
  • 4. Department of Obstetrics and Gynaecology, Obstetrics Diagnostics and Therapeutics Group, The University of Melbourne and Mercy Hospital for Women, Heidelberg, Australia.
  • 5. School of Biomedical Sciences, The University of Queensland, Brisbane, Australia.
  • 6. Department of Obstetrics and Gynaecology, Diagnostics Discovery and Reverse Translation in Pregnancy Group, The University of Melbourne and Mercy Hospital for Women, Heidelberg, Australia.
  • 7. Department of Obstetrics and Gynaecology, The Ritchie Centre, School of Clinical Sciences, Monash University and The Hudson Institute of Medical Research, Clayton, Australia.
PMID: 36260752 DOI: 10.26508/lsa.202201517
Abstract

Preeclampsia affects ∼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(ω)-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 preeclampsia during pregnancy, it does not appear to model the adverse increase in Cardiovascular Disease risk seen in individuals after preeclampsia.

Products