Vitamin D induces increased systolic arterial pressure via vascular reactivity and mechanical properties.

Priscila Portugal Dos Santos,Bruna Paola Murino Rafacho,Rita De Cássia Tostes,Marcos Ferreira Minicucci,Meliza Goi Roscani,Marcondes Alves Barbosa Silva,Sergio Alberto Rupp De Paiva,Leonardo Antonio Memede Zornoff,Rodrigo Gibin Jaldin,Stêfany Bruno Assis Cau,Andréa De Freitas Gonçalves,Paula Schimdt Azevedo,Thiago Bruder Do Nascimento

doi:10.1371/journal.pone.0098895

Vitamin D induces increased systolic arterial pressure via vascular reactivity and mechanical properties.

Priscila Portugal Dos Santos, Bruna Paola Murino Rafacho + Show 11 more

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https://doi.org/10.1371/journal.pone.0098895

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Abstract

Background/AimsThe 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.MethodsMale 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.ResultsSAP 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.ConclusionOur 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.

Highlights

Vitamin D (VD) is a fat-soluble compound primarily obtained through cutaneous synthesis
The daily intake of VD and serum calcium and phosphorus were higher in supplemented groups compared to control
Systolic arterial pressure was higher in both the supplemented groups compared to the control

Summary

Introduction

Vitamin D (VD) is a fat-soluble compound primarily obtained through cutaneous synthesis. The prevalence of VD deficiency has increased in recent years [3], becoming a public health problem worldwide [4]. It is estimated that one billion people worldwide are either VD insufficient or deficient [3]. Researchers have recommended increased sun exposure, food fortification and VD supplementation, both for people at higher risk for hypovitaminosis D and for the general population [12,13,14]. Medium and long term effects of VD supplementation with doses above 4,000 IU/day are not well known, and risks may not be disregarded, toxic effects are rare [15]. VD dose of 4,000 IU/day was recently recommended by Institute of Medicine as Upper Level Intake [16]

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