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

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Item Type:	Article
Title:	Vitamin D supplementation reduces some AT1-AA induced downstream targets implicated in preeclampsia including hypertension
Creators Name:	Faulkner, J.L., Amaral, L.M., Cornelius, D.C., Cunningham, M.W., Ibrahim, T., Heep, A., Campbell, N., Usry, N., Wallace, K., Herse, F., Dechend, R. and LaMarca, B.D.
Abstract:	Autoantibodies to the angiotensin II (ANGII) 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 if the decrease in AT1-AA was the mechanism whereby Vitamin D lowered MAP or if it was through factors downstream of AT1-AA. Uterine artery resistance index, placental ET-1 and sFlt-1 are increased with AT1-AA induced hypertension and 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 ANGII (50ng/kg/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 GD14-18. MAP (mmHg) increased in AT1-AA (121±4) and ANGII (113±1) infused pregnant rats compared to normal pregnant rats (NP) (101±2) but was lower in AT1-AA+VD2 (105±2), AT1-AA+VD3 (109±2), ANGII+VD2 (104±4) and ANGII+VD3 (104±3). VD2 and/or VD3 improved PE features associated with AT1-AA during pregnancy, while ANGII did not induce such features, supporting the hypothesis that AT1-AA induces PE features during pregnancy and these are improved with Vit 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:	Blood Pressure, Dietary Supplements, Drug Dose-Response Relationship, Oral Administration, Pre-Eclampsia, Pregnancy, Sprague-Dawley Rats, Treatment Outcome, Type 1 Angiotensin Receptor, Vitamin D, Animals, Rats
Source:	American Journal of Physiology Regulatory Integrative and Comparative Physiology
ISSN:	0363-6119
Publisher:	American Physiological Society
Volume:	312
Number:	1
Page Range:	R125-R131
Date:	1 January 2017
Official Publication:	https://doi.org/10.1152/ajpregu.00218.2016
External Fulltext:	View full text on PubMed Central
PubMed:	View item in PubMed

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