title: Vitamin D supplementation improves pathophysiology in a rat model of preeclampsia.
abstract: Deficiency of vitamin D (VD) is associated with preeclampsia (PE), a hypertensive disorder of pregnancy characterized by proinflammatory immune activation. We sought to determine whether VD supplementation would reduce the pathophysiology and hypertension associated with the reduced uterine perfusion pressure (RUPP) rat model of PE. Normal pregnant (NP) and RUPP rats were supplemented with VD2 or VD3 (270 IU and 15 IU/day, respectively) on gestation days 14-18 and mean arterial pressures (MAPs) measured on day 19. MAP increased in RUPP to 123 ± 2 mmHg compared with 102 ± 3 mmHg in NP and decreased to 113 ± 3 mmHg with VD2 and 115 ± 3 mmHg with VD3 in RUPP rats. Circulating CD4+ T cells increased in RUPP to 7.90 ± 1.36% lymphocytes compared with 2.04 ± 0.67% in NP but was lowered to 0.90 ± 0.19% with VD2 and 4.26 ± 1.55% with VD3 in RUPP rats. AT1-AA, measured by chronotropic assay, decreased from 19.5 ± 0.4 bpm in RUPPs to 8.3 ± 0.5 bpm with VD2 and to 15.4 ± 0.7 bpm with VD3. Renal cortex endothelin-1 (ET-1) expression was increased in RUPP rats (11.6 ± 2.1-fold change from NP) and decreased with both VD2 (3.3 ± 1.1-fold) and VD3 (3.1 ± 0.6-fold) supplementation in RUPP rats. Plasma-soluble FMS-like tyrosine kinase-1 (sFlt-1) was also reduced to 74.2 ± 6.6 pg/ml in VD2-treated and 91.0 ± 16.1 pg/ml in VD3-treated RUPP rats compared with 132.7 ± 19.9 pg/ml in RUPP rats. VD treatment reduced CD4+ T cells, AT1-AA, ET-1, sFlt-1, and blood pressure in the RUPP rat model of PE and could be an avenue to improve treatment of hypertension in response to placental ischemia.
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: Denise C
authors.initials: DC
authors.lastname: Cornelius
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: Ashlyn C
authors.initials: AC
authors.lastname: Harmon
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 Obstetrics and Gynecology, University of Mississippi Medical Center, Jackson, Mississippi;
authors.forename: Marie M
authors.initials: MM
authors.lastname: Darby
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: D'Andrea S
authors.initials: DS
authors.lastname: Thomas
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.
authors.forename: Gerd
authors.initials: G
authors.lastname: Wallukat
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; Department of Obstetrics and Gynecology, University of Mississippi Medical Center, Jackson, Mississippi; bblamarca@umc.edu.
authors.forename: Babbette
authors.initials: B
authors.lastname: LaMarca
mesh_terms: D000818:Animals; D062186:Arterial Pressure / Q000187:drug effects; D001724:Birth Weight / Q000187:drug effects; D015496:CD4-Positive T-Lymphocytes; D019587:Dietary Supplements; D019332:Endothelin-1 / Q000096:biosynthesis; D005260:Female; D007511:Ischemia / Q000188:drug therapy / Q000378:metabolism; D007668:Kidney / Q000378:metabolism; D018655:Lymphocyte Count; D011225:Pre-Eclampsia / Q000188:drug therapy* / Q000503:physiopathology*; D011247:Pregnancy; D051381:Rats; D044140:Receptor, Angiotensin, Type 1 / Q000096:biosynthesis; D012039:Regional Blood Flow / Q000187:drug effects; D014599:Uterus / Q000503:physiopathology; D040281:Vascular Endothelial Growth Factor Receptor-1 / Q000378:metabolism; D014807:Vitamin D / Q000097:blood / Q000627:therapeutic use*; D014815:Vitamins / Q000097:blood / Q000627:therapeutic use*
chemical_list: D019332:Endothelin-1; D044140:Receptor, Angiotensin, Type 1; D014815:Vitamins; D014807:Vitamin D; C501164:Flt1 protein, rat; D040281:Vascular Endothelial Growth Factor Receptor-1
keywords: hypertension; immune activation; preeclampsia; vitamin D