Abstract P091: Vitamin D Supplementation Inhibits Blood Pressure and Uterine Artery Resistance Induced by Autoantibodies to the AT1 Receptor
Studies in our lab have previously shown that Vitamin D supplementation in the RUPP rat model of preeclampsia lowers blood pressure and reduces autoantibodies to the AT1 receptor (AT1-AA). Therefore, we sought to determine if the effects of Vitamin D supplementation to inhibit endothelial dysfunction and hypertension during pregnancy were mediated by AT1-AA reduction. We hypothesized that Vitamin D supplementation to AT1-AA-induced hypertensive pregnant rats would reduce anti-angiogenic factor soluble FMS-like tyrosine kinase-1 (sflt-1) and uterine artery resistance index (UARI) while improving blood pressure (MAP). Purified rat AT1-AA was infused (1:40) into Sprague-Dawley rats via miniosmotic pump from gestational day (GD) 12 to GD19. On GD14-18 we administered Vitamin D2 or D3 (VD2 or VD3) to AT1-AA rats (50ul/ml) by oral gavage. On GD18 indwelling carotid catheters were inserted and UARI assessed by Doppler sonography and MAP was measured on GD19. Consistent with previous studies, MAP was 119.0 mmHg in AT1-AA infused pregnant rats. MAP was unchanged with VD2 treatment at 121.7 mmHg (n=3), however, reduced to 109.3 mmHg (n=3) in AT1-AA+VD3 rats. Pup and placental weights were 1.79 and 0.46 g (n=3), respectively, in AT1-AA rats and were increased with VD2 treatment to 2.33 and 0.54 g (n=3) and to 2.39 and 0.56 g (n=3) in AT1-AA+VD3 rats. UARI was 0.577 (n=2) in AT1-AA rats but reduced with VD2 treatment to 0.491 (n=3) and VD3 to 0.452 (n=2). Plasma sflt-1, which is increased with AT1-AA infusion, was measured with ELISA and was >1050 pg/ml in AT1-AA rats (n=3) and greatly reduced in both AT1-AA+VD2 at 42.3 pg/ml (n=2) and AT1-AA+VD3 at 241.0 pg/ml (n=3). Our preliminary data demonstrate that Vitamin D supplementation improves uterine artery vascular resistance and sflt-1 and that these are potential mechanisms for improving fetal weight and hypertension that is induced by AT1-AA during pregnancy.
Author Disclosures: J.L. Faulkner: None. M.W. Cunningham: None. L.M. Amaral: None. T. Ibrahim: None. D.C. Cornelius: None. D.S. Thomas: None. G. Wallukat: None. R. Dechend: None. B. LaMarca: B. Research Grant (includes principal investigator, collaborator, or consultant and pending grants as well as grants already received); Significant; NIH.
- © 2015 by American Heart Association, Inc.