Oral Presentation ESA-SRB-APEG-NZSE 2022

C-type natriuretic peptide relaxes omental arteries in a new ex vivo model of preeclampsia. (#185)

Bianca R Fato 1 2 3 4 , Natasha de Alwis 1 2 3 4 , Sally Beard 1 2 3 4 , Hobbs J Adrian 5 , Tu'uhevaha J Kaitu'u-Lino 2 3 4 , Kristen J Bubb 6 , Natalie J Hannan 1 2 3 4
  1. Therapeutics Discovery and Vascular Function Group, Heidelberg, Victoria, Australia
  2. University of Melbourne, Parkville, VICTORIA, Australia
  3. Department of Obstetrics and Gynaecology , University of Melbourne, Parkville, Victoria, Australia
  4. Mercy Hospital for Women, Heidelberg, Victoria, Australia
  5. Queen Mary University of London, London, England
  6. Department of Physiology, Monash University, Clayton, Victoria, Australia

Preeclampsia is a serious pregnancy complication, associated with widespread maternal vascular dysfunction. C-type natriuretic peptide (CNP) contributes to vascular homeostasis, acting through NPR-B and NPR-C receptors; however the role of CNP in preeclampsia is unknown. This study characterises the expression of CNP during pregnancy and investigates whether CNP can dilate maternal arteries in several ex vivo models of preeclampsia.

 

CNP, NPR-B and NPR-C mRNA expression was assessed in placental tissue (preterm n=86; term n=49) and omental arteries (n=17) from preeclamptic and normotensive pregnancies via qPCR. Human primary cytotrophoblasts (n=3) and placental explants (n=5) were cultured under normoxic (8% O2) or hypoxic (1% O2) conditions and mRNA expression was assessed. Using wire myography, we investigated the effects of CNP on dilation of omental arteries dissected from fat biopsies, collected during caesarean section of healthy pregnancies (n=22). Arteries were pre-constricted with serum from preeclamptic patients, or recombinant endothelin-1 (vasoconstrictor high in preeclampsia) to model vasoconstriction associated with preeclampsia. Pre-constricted arteries were then treated with synthetic CNP (0.001-100uM), or vehicle, and vascular relaxation assessed. In further studies, arteries were pre-incubated with NPR-B or NPR-C antagonists prior to serum-induced constriction, investigating the mechanistic signalling within the model.

 

The mRNA expression of CNP, NPR-B and NPR-C was not altered in placenta or omental arteries from preeclamptic pregnancies compared to normotensive controls. Moreover, NPR-C was undetected in cytotrophoblasts, and hypoxia did not alter placental expression of CNP. Furthermore, CNP directly stimulated maternal artery vasorelaxation in an innovative model of preeclampsia (constriction driven by serum). However, its actions were not attributed to NPR-C receptor signalling, nor endothelin-1 driven constriction pathways.

 

This study demonstrated that CNP expression is not altered in the placenta or maternal vasculature in preeclampsia. However, collectively the data suggest that enhancing CNP could offer a therapeutic strategy for reducing systemic vascular constriction in preeclampsia.