Vitamin D Lowers Blood Pressure, ET‐1 and sFlt‐1 in AT1 Autoantibody Induced Hypertension During Pregnancy

Abstract

Autoantibodies to the angiotensin II type I receptor (AT1‐AA) play a role in hypertension associated with preeclampsia (PE). We found that Vitamin D (VD) reduces AT1‐AA and blood pressure (MAP) in a rat model of PE. Here we tested the hypothesis that VD would improve MAP and endothelial dysfunction markers associated with AT1‐AA during PE. We infused AT1‐AA (1:40 in saline) via osmotic minipump on gestational day (GD) 12–19 in pregnant rats. Either VD2 (270 IU/day) or VD3 (15 IU/day) were given on GD14–18 by oral gavage. Uterine artery resistance index (UARI) was measured by Doppler sonography on GD18 and MAP measured on GD19 by indwelling catheter. MAP increased in AT1‐AA (121±4 mmHg) compared to normal pregnant (NP) (101±2) but was decreased in AT1‐AA+VD2 (105±2) and AT1‐AA+VD3 (109±2). UARI increased in AT1‐AA rats to 0.57±0.01 compared to NP (0.41±0.02). VD3 reduced UARI to 0.49±0.03. Placental preproendothelin‐1 (ET‐1) mRNA expression increased in AT1‐AA (18.1±2.9‐fold) from NP and was decreased with VD2 (4.3±1.4) and VD3 (1.3±0.3). Plasma 8‐isoprostanes (ROS) increased in AT1‐AA to 1633±179 pg/ml compared to NP (634±197) but was decreased with VD2 (436±81) and VD3 (752±94). sFlt‐1 increased in AT1‐AA (715±189 pg/ml) compared to NP (94±12) and was reduced with both VD2 (77±16) and VD3 (195±7). We have demonstrated that VD improved ET‐1, ROS and sFlt‐1 in response to AT1‐AA in pregnant rats. We believe reducing these factors led to reduced vascular resistance and MAP responses commonly seen in elevated AT1‐AA, as in the case of PE, thereby supporting a role for VD supplementation as a prevention for PE.Support or Funding InformationProject funded by NIH RO1HD067541 and T32HL105324