Vitamin D supplementation improves pathophysiology in a rat model of preeclampsia

Deficiency of Vitamin D (VD) is associated with preeclampsia (PE), a hypertensive disorder of pregnancy characterized by proinflammatory immune activation. We sought to determine if VD supplementation would reduce the pathophysiology and hypertension associated with the Reduced Uterine Perfusion Pressure (RUPP) rat model of PE. Normal pregnant (NP) and RUPP rats were supplemented with VD2 or VD3 (270 IU and 15 IU/day, respectively) on gestation days 14-18 and mean arterial pressures (MAPs) measured on day 19. MAP increased in RUPP to 123+/-2 mmHg compared to 102+/-3 mmHg in NP and decreased to 113+/-3 mmHg with VD2 and 115+/-3 mmHg with VD3 in RUPP rats. Circulating CD4+ T cells increased in RUPP to 7.90+/-1.36% lymphocytes compared to 2.04+/-0.67% in NP but was lowered to 0.90+/-0.19% with VD2 and 4.26+/-1.55% with VD3 in RUPP rats. AT1-AA, measured by chronotropic assay, decreased from 19.5+/-0.4 bpm in RUPPs to 8.3+/-0.5 bpm with VD2 and 15.4±0.7 bpm with VD3. Renal cortex endothelin-1 (ET-1) expression was increased in RUPP rats (11.6+/-2.1-fold change from NP) and decreased with both VD2 (3.3+/-1.1-fold) and VD3 (3.1+/-0.6-fold) supplementation in RUPP rats. Plasma soluble FMS-like tyrosine kinase-1 (sFlt-1) was also reduced to 74.2+/-6.6 pg/ml in VD2-treated and 91.0+/-16.1 pg/ml in VD3-treated RUPP rats compared to 132.7+/-19.9 pg/ml in RUPP rats. VD treatment reduced CD4+ T cells, AT1-AA, ET-1, sFlt-1, and blood pressure in the RUPP rat model of PE and could be an avenue to improve treatment of hypertension in response to placental ischemia.