Vitamin D supplementation reduces some AT 1 -AA-induced downstream targets implicated in preeclampsia including hypertension

Jessica L Faulkner, Lorena M Amaral, Denise C Cornelius, Mark W Cunningham, Tarek Ibrahim, Autumn Heep, Nathan Campbell, Nathan Usry, Kedra Wallace, Florian Herse, Ralf Dechend, Babbette LaMarca
American Journal of Physiology - Regulatory, Integrative and Comparative Physiology2017
Autoantibodies to the ANG II 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 whether the decrease in AT1 -AA was the mechanism whereby vitamin D lowered MAP or if it were through factors downstream of AT1 -AA. Uterine artery resistance index, placental ET-1, and soluble FMS-like tyrosine kinase-1 are increased with AT1 -AA-induced hypertension and are 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 ANG II (50 ng·kg?1 ·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–GD18. MAP (mmHg) increased in AT1 -AA (121 ? 4) and ANG II (113? 1)-infused preg- nant rats compared with normal pregnant rats (NP) (101? 2) but was lower in AT1 -AA?VD2 (105? 2), AT1 -AA?VD3 (109? 2), ANG II?VD2 (104 ? 4), and ANG II?VD3 (104? 3). VD2 and/or VD3 improved PE features associated with AT1 -AA during pregnancy, while ANG II did not induce such features, supporting the hypothesis that AT1 -AA induces PE features during pregnancy, and these are improved with vitamin 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.
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