Endocrine Abstracts

Introduction: The renin-angiotensin system (RAS) become upregulated very early on in pregnancy and is crucial in maintaining blood pressure. In addition to the peripheral RAS there is a uteroplacental RAS, which is also important in regulating placental function and development. Recent work has shown extra-renal sodium storage in the skin; it is suggested that the placenta may also function as a salt sensing organ and is important in regulating maternal blood pressure.

Objectives: To test the hypothesis that increased sodium leads to a decrease in expression of RAS components involved in vasoconstriction and increased expression of those components involved in vasodilation.

Methods: The human choriocarcinoma cell lines BeWo and JEG3 were incubated in medium containing 110 mM (control), 140 mM or 170 mM Na⁺ (in the form of NaCl). Cells were harvested after 6 hour incubation and RNA was extracted. TaqMan PCR was performed to determine mRNA expression of renin, (pro)renin receptor (PRR), angiotensinogen (AGT), angiotensin-converting enzyme (ACE), angiotensin-II receptor type 1 or 2 (AGTR1, AGTR2), and mineralocorticoid receptor (MR). Relative quantification was performed and results normalised to the housekeeping gene cyclophilin A.

Results: Following NaCl incubation decreased mRNA expression was found for MR (0.4 fold, P<0.001 in BeWo; 0.5 fold, P<0.001 in JEG3 at 170 mM) and AGT (0.5 fold, P<0.001 in BeWo; 0.7 fold, P<0.05 in JEG3 at 170 mM). ACE mRNA expression was low in both BeWo and JEG3 but increased following NaCl treatment (1.5 fold, P<0.05 in BeWo; 150-fold, P<0.05 in JEG3 at 170 mM). mRNA expression of PRR was not found to differ in either BeWo or JEG3 cells following NaCl treatment. Renin, AGTR1 and AGTR2 mRNA expression was not detected in either cell line.

Conclusion: This study is the first to show that Na⁺ effects placental mRNA expression of MR, AGT and ACE. Therefore the placenta could be acting as a salt sensitive site and may be involved in the regulation of maternal blood pressure regulation. Further work is needed to confirm if these mRNA changes are translated to functional changes and also if they can be replicated in isolated human primary trophoblast cells.