title: Vitamin D supplementation reduces some AT1-AA-induced downstream targets implicated in preeclampsia including hypertension.
abstract: 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 pregnant 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.
authors.affiliation: Department of Pharmacology and Toxicology, University of Mississippi Medical Center, Jackson, Mississippi.
authors.forename: Jessica L
authors.initials: JL
authors.lastname: Faulkner
authors.affiliation: Department of Pharmacology and Toxicology, University of Mississippi Medical Center, Jackson, Mississippi.
authors.forename: Lorena M
authors.initials: LM
authors.lastname: Amaral
authors.affiliation: Department of Pharmacology and Toxicology, University of Mississippi Medical Center, Jackson, Mississippi.
authors.forename: Denise C
authors.initials: DC
authors.lastname: Cornelius
authors.affiliation: Department of Pharmacology and Toxicology, University of Mississippi Medical Center, Jackson, Mississippi.
authors.forename: Mark W
authors.initials: MW
authors.lastname: Cunningham
authors.affiliation: Department of Pharmacology and Toxicology, University of Mississippi Medical Center, Jackson, Mississippi.
authors.forename: Tarek
authors.initials: T
authors.lastname: Ibrahim
authors.affiliation: Department of Pharmacology and Toxicology, University of Mississippi Medical Center, Jackson, Mississippi.
authors.forename: Autumn
authors.initials: A
authors.lastname: Heep
authors.affiliation: Department of Pharmacology and Toxicology, University of Mississippi Medical Center, Jackson, Mississippi.
authors.forename: Nathan
authors.initials: N
authors.lastname: Campbell
authors.affiliation: Department of Pharmacology and Toxicology, University of Mississippi Medical Center, Jackson, Mississippi.
authors.forename: Nathan
authors.initials: N
authors.lastname: Usry
authors.affiliation: Department of Obstetrics and Gynecology, University of Mississippi Medical Center, Jackson, Mississipppi.
authors.forename: Kedra
authors.initials: K
authors.lastname: Wallace
authors.affiliation: Experimental and Clinical Research Center, Charité Campus Buch and Max-Delbrück Center for Molecular Medicine, Berlin, Germany; and.
authors.forename: Florian
authors.initials: F
authors.lastname: Herse
authors.affiliation: Experimental and Clinical Research Center, Charité Campus Buch and Max-Delbrück Center for Molecular Medicine, Berlin, Germany; and.|HELIOS Clinic, Department of Cardiology and Nephrology, Berlin, Germany.
authors.forename: Ralf
authors.initials: R
authors.lastname: Dechend
authors.affiliation: Department of Pharmacology and Toxicology, University of Mississippi Medical Center, Jackson, Mississippi; bblamarca@umc.edu.|Department of Obstetrics and Gynecology, University of Mississippi Medical Center, Jackson, Mississipppi.
authors.forename: Babbette
authors.initials: B
authors.lastname: LaMarca
mesh_terms: D000284:Administration, Oral; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects / Q000276:immunology*; D019587:Dietary Supplements; D004305:Dose-Response Relationship, Drug; D005260:Female; D011225:Pre-Eclampsia / Q000188:drug therapy* / Q000503:physiopathology*; D011247:Pregnancy; D051381:Rats; D017207:Rats, Sprague-Dawley; D044140:Receptor, Angiotensin, Type 1 / Q000276:immunology*; D016896:Treatment Outcome; D014807:Vitamin D / Q000008:administration & dosage*
chemical_list: D044140:Receptor, Angiotensin, Type 1; D014807:Vitamin D
keywords: hypertension; inflammation; pregnancy