Stimulation of Angiotensin II Receptor Subtype 2 Reduces Preeclampsia-like Symptoms in a Mouse Model of Preeclampsia

TL;DR

Stimulating a specific receptor in mice reduced preeclampsia-like symptoms, suggesting a potential new treatment for the condition.

Contribution

This study is the first to demonstrate that activating the AT2R receptor reduces preeclampsia-like symptoms in a mouse model.

Findings

C21 reduced plasma sFlt-1 concentration and ameliorated hypertension in the mouse model of preeclampsia.

C21 did not alter the splenic T and B cell profiles in the model mice.

sFlt-1 levels were significantly reduced in mice treated with C21.

Abstract

Angiotensin II (AngII) receptor subtype 1 (AT1R) is involved in the pathogenesis of preeclampsia (PE). Angiotensin II receptor subtype 2 (AT2R) can antagonize the effects of AT1R, but its effects during pregnancy are not known. We investigated the effect of AT2R on the pathogenesis of PE using a mouse model and recently developed AT2R agonist (compound 21 [C21]). Blastocysts collected from pregnant imprinting control region (ICR) mice were incubated with adenovirus containing the CD40L gene and transferred into the uterine horns of pseudo-pregnant ICR mice to express PE-like features. Osmotic pumps were placed subcutaneously on the dorsal side with C21 or saline. C21 reduced the plasma soluble fms-like tyrosine kinase 1 (sFlt-1) concentration, ameliorating hypertension. The splenic T and B cell profiles in model mice were analyzed by flow cytometry. The gated percentage of IFN-γ-positive Th cells was significantly increased and the percentage of plasma cells in B cells was significantly decreased; however, the percentages were not altered by C21. sFlt-1 and soluble endoglin concentrations in plasma were measured with an enzyme-linked immunosorbent assay, and sFlt-1 was reduced. C21 could become a candidate PE drug as it ameliorated the pathophysiology of PE as a result of decreased production of sFlt-1.

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