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

Item Type:Article
Title:Vitamin D supplementation reduces some AT1-AA induced downstream targets implicated in preeclampsia including hypertension
Creators Name:Faulkner, J.L. and Amaral, L.M. and Cornelius, D.C. and Cunningham, M.W. and Ibrahim, T. and Heep, A. and Campbell, N. and Usry, N. and Wallace, K. and Herse, F. and 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 (U.S.A.)
Volume:312
Number:1
Page Range:R125-R131
Date:1 January 2017
Official Publication:https://doi.org/10.1152/ajpregu.00218.2016
PubMed:View item in PubMed

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