Vitamin D supplementation reduces some AT1-AA-induced downstream targets implicated in preeclampsia including hypertension

Abstract

Autoantibodies to the ANG II type I receptor (AT₁-AA) are associated with preeclampsia (PE). We found that vitamin D supplementation reduced AT₁-AA and blood pressure (MAP) in the RUPP rat model of PE. However, it was undetermined whether the decrease in AT₁-AA was the mechanism whereby vitamin D lowered MAP or if it were through factors downstream of AT₁-AA. Uterine artery resistance index, placental ET-1, and soluble FMS-like tyrosine kinase-1 are increased with AT₁-AA-induced hypertension and are considered markers of PE in pregnant women. Therefore, we hypothesized that vitamin D would reduce PE factors during AT₁-AA-induced hypertension and could lower blood pressure in a model of hypertension during pregnancy without PE features. Either ANG II (50 ng·kg^-1·day) or AT₁-AA (1:40) was infused from gestational day (GD) 12-19. vitamin D₂ (VD2, 270 IU/day) or vitamin D₃ (VD3, 15 IU/day) was administered orally from GD14-GD18. MAP (mmHg) increased in AT₁-AA (121 ± 4) and ANG II (113 ± 1)-infused pregnant rats compared with normal pregnant rats (NP) (101 ± 2) but was lower in AT₁-AA+VD2 (105 ± 2), AT₁-AA+VD3 (109 ± 2), ANG II+VD2 (104 ± 4), and ANG II+VD3 (104 ± 3). VD2 and/or VD3 improved PE features associated with AT₁-AA during pregnancy, while ANG II did not induce such features, supporting the hypothesis that AT₁-AA induces PE features during pregnancy, and these are improved with vitamin D. In this study, we demonstrate that vitamin D improved many factors associated with PE and reduced blood pressure in a hypertensive model without PE features, indicating that vitamin D could be beneficial for various hypertensive disorders of pregnancy.

Keywords: hypertension; inflammation; pregnancy.