Abstract 292: Vitamin D Supplementation Reduces CD4+ T Cells, Blood Pressure and Autoantibodies to the AT1 Receptor (AT1-AA) in a Rat Model of Preeclampsia
Preeclampsia (PE) is characterized by the development of hypertension, endothelial dysfunction and chronic immune activation after 20 weeks of gestation. PE women exhibit elevated CD4+ T cells, proinflammatory cytokines and agonistic autoantibodies to the angiotensin II type I receptor (AT1-AA). Vitamin D deficiency is associated with increased prevalence of hypertension and chronic inflammatory diseases both in the presence and absence of pregnancy. We utilize the Reduced Uterine Perfusion Pressure (RUPP) model of PE in the pregnant rat which exhibits hypertension, endothelial dysfunction as well as increased CD4+ T cells, inflammatory cytokines and AT1-AA. Therefore, we tested the hypothesis that administration of exogenous Vitamin D2 (VD2) and Vitamin D3 (VD3) would ameliorate hypertension and or chronic inflammation associated with placental ischemia in the RUPP rat. For these studies, the RUPP procedure was performed on gestation day 14 (GD14) and normal pregnant (NP) and RUPP rats were treated daily with 50uM VD2 or VD3 via oral gavage on GD14-18. Carotid catheters were inserted on GD18 and blood pressure (MAP), blood and tissues were collected on GD19. Flow cytometry was used to evaluate CD4+ T cells in control RUPP rats and RUPP rats treated with Vitamin D. On GD19, MAP was increased in RUPP rats to 123 ± 3.5 compared to 108.8 ± 4.3 mmHg in NP rats (n=5-6, p<0.05). Supplementation with either VD2 or VD3 lowered MAP to 113 ± 6.9 or 115.4 ± 2.3 mmHg, respectively (n=4-5). CD4+ T cells in RUPP compared to NP rats increased from 2.80 ± 0.95 to 8.49 ± 1.52 percent (n=8-11, p<0.05). Circulating CD4+ T cells fell to 1.22 ± 0.41 percent with VD2 and to 4.59 ± 3.67 percent with VD3 (n=2-3). AT1-AA levels, measured via chronotropic response in cardiomyocytes, were 19.50 ± 0.44 beats/min in RUPP rats and decreased to 15.35 ± 0.69 with VD3, and further to 8.33 ± 0.51 with VD2 supplementation (n=5, p<0.05). Taken together, these data indicate that pharmaceutical Vitamin D supplementation reduced blood pressure and markers of chronic inflammation in a rat model of PE, thereby suggesting a role for Vitamin D supplementation to improve hypertension and chronic inflammation in response to diseases associated with placental ischemia, such as PE.
Author Disclosures: J.L. Faulkner: None. M.M. Darby: None. D.C. Cornelius: None. J. Moseley: None. F. Herse: None. R. Dechend: None. B. LaMarca: None.
- © 2014 by American Heart Association, Inc.