title: Vitamin D induces increased systolic arterial pressure via vascular reactivity and mechanical properties.
abstract: OBJECTIVE
  The aim of this study was to evaluate whether supplementation of high doses of cholecalciferol for two months in normotensive rats results in increased systolic arterial pressure and which are the mechanisms involved. Specifically, this study assesses the potential effect on cardiac output as well as the changes in aortic structure and functional properties.
  
  
  METHODS
  Male Wistar rats were divided into three groups: 1) Control group (C, n = 20), with no supplementation of vitamin D, 2) VD3 (n = 19), supplemented with 3,000 IU vitamin D/kg of chow; 3) VD10 (n = 21), supplemented with 10,000 IU vitamin D/kg of chow. After two months, echocardiographic analyses, measurements of systolic arterial pressure (SAP), vascular reactivity, reactive oxygen species (ROS) generation, mechanical properties, histological analysis and metalloproteinase-2 and -9 activity were performed.
  
  
  RESULTS
  SAP was higher in VD3 and VD10 than in C rats (p = 0.001). Echocardiographic variables were not different among groups. Responses to phenylephrine in endothelium-denuded aortas was higher in VD3 compared to the C group (p = 0.041). Vascular relaxation induced by acetylcholine (p = 0.023) and sodium nitroprusside (p = 0.005) was impaired in both supplemented groups compared to the C group and apocynin treatment reversed impaired vasodilation. Collagen volume fraction (<0.001) and MMP-2 activity (p = 0.025) was higher in VD10 group compared to the VD3 group. Elastin volume fraction was lower in VD10 than in C and yield point was lower in VD3 than in C.
  
  
  CONCLUSIONS
  Our findings support the view that vitamin D supplementation increases arterial pressure in normotensive rats and this is associated with structural and functional vascular changes, modulated by NADPH oxidase, nitric oxide, and extracellular matrix components.
authors.affiliation: Department of Internal Medicine, Botucatu Medical School, UNESP - Universidade Estadual Paulista, Botucatu, São Paulo, Brazil.
authors.forename: Priscila Portugal Dos
authors.initials: PP
authors.lastname: Santos
authors.affiliation: Department of Internal Medicine, Botucatu Medical School, UNESP - Universidade Estadual Paulista, Botucatu, São Paulo, Brazil.
authors.forename: Bruna Paola Murino
authors.initials: BP
authors.lastname: Rafacho
authors.affiliation: Department of Internal Medicine, Botucatu Medical School, UNESP - Universidade Estadual Paulista, Botucatu, São Paulo, Brazil.
authors.forename: Andréa de Freitas
authors.initials: Ade F
authors.lastname: Gonçalves
authors.affiliation: Department of Surgery and Orthopaedics, Botucatu Medical School, UNESP - Universidade Estadual Paulista, Botucatu, São Paulo, Brazil.
authors.forename: Rodrigo Gibin
authors.initials: RG
authors.lastname: Jaldin
authors.affiliation: Department of Pharmacology, School of Medicine at Ribeirao Preto - USP, University of São Paulo, São Paulo, Brazil.
authors.forename: Thiago Bruder do
authors.initials: TB
authors.lastname: Nascimento
authors.affiliation: Department of Pharmacology, School of Medicine at Ribeirao Preto - USP, University of São Paulo, São Paulo, Brazil.
authors.forename: Marcondes Alves Barbosa
authors.initials: MA
authors.lastname: Silva
authors.affiliation: Department of Pharmacology, School of Medicine at Ribeirao Preto - USP, University of São Paulo, São Paulo, Brazil.
authors.forename: Stêfany Bruno Assis
authors.initials: SB
authors.lastname: Cau
authors.affiliation: Department of Internal Medicine, Botucatu Medical School, UNESP - Universidade Estadual Paulista, Botucatu, São Paulo, Brazil.
authors.forename: Meliza Goi
authors.initials: MG
authors.lastname: Roscani
authors.affiliation: Department of Internal Medicine, Botucatu Medical School, UNESP - Universidade Estadual Paulista, Botucatu, São Paulo, Brazil.
authors.forename: Paula Schimdt
authors.initials: PS
authors.lastname: Azevedo
authors.affiliation: Department of Internal Medicine, Botucatu Medical School, UNESP - Universidade Estadual Paulista, Botucatu, São Paulo, Brazil.
authors.forename: Marcos Ferreira
authors.initials: MF
authors.lastname: Minicucci
authors.affiliation: Department of Pharmacology, School of Medicine at Ribeirao Preto - USP, University of São Paulo, São Paulo, Brazil.
authors.forename: Rita de Cássia
authors.initials: Rde C
authors.lastname: Tostes
authors.affiliation: Department of Internal Medicine, Botucatu Medical School, UNESP - Universidade Estadual Paulista, Botucatu, São Paulo, Brazil.
authors.forename: Leonardo Antonio Memede
authors.initials: LA
authors.lastname: Zornoff
authors.affiliation: Department of Internal Medicine, Botucatu Medical School, UNESP - Universidade Estadual Paulista, Botucatu, São Paulo, Brazil.
authors.forename: Sergio Alberto Rupp de
authors.initials: SA
authors.lastname: Paiva
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D001011:Aorta / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D001794:Blood Pressure / Q000187:drug effects*; D002762:Cholecalciferol / Q000008:administration & dosage / Q000494:pharmacology*; D003094:Collagen / Q000235:genetics / Q000378:metabolism; D019587:Dietary Supplements; D004549:Elastin / Q000235:genetics / Q000378:metabolism; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000235:genetics / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000235:genetics / Q000378:metabolism; D009599:Nitroprusside / Q000494:pharmacology; D010656:Phenylephrine / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D017382:Reactive Oxygen Species / Q000378:metabolism; D014664:Vasodilation / Q000187:drug effects*; D014665:Vasodilator Agents / Q000494:pharmacology; D014815:Vitamins / Q000008:administration & dosage / Q000494:pharmacology*
chemical_list: D017382:Reactive Oxygen Species; D014665:Vasodilator Agents; D014815:Vitamins; D009599:Nitroprusside; D002762:Cholecalciferol; D010656:Phenylephrine; D003094:Collagen; D004549:Elastin; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9; D000109:Acetylcholine