folder

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

Authors

  • J.L. Faulkner
  • L.M. Amaral
  • D.C. Cornelius
  • M.W. Cunningham
  • T. Ibrahim
  • A. Heep
  • N. Campbell
  • N. Usry
  • K. Wallace
  • F. Herse
  • R. Dechend
  • B.D. LaMarca

Journal

  • American Journal of Physiology Regulatory Integrative and Comparative Physiology

Citation

  • Am J Physiol Regul Integr Comp Physiol 312 (1): R125-R131

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.


DOI

doi:10.1152/ajpregu.00218.2016