Vitamin D supplementation alters the expression of genes associated with hypertension and did not induce DNA damage in rats

ABSTRACT

Vitamin D3 deficiency has been correlated with altered expression of genes associated with increased blood pressure (BP); however, the role of vitamin D3 supplementation in the genetic mechanisms underlying hypertension remains unclear. Thus, the aim of this study was investigate the consequences of vitamin D3 supplemented (10,000 IU/kg) or deficient (0 IU/kg) diets on regulation of expression of genes related to hypertension pathways in heart cells of spontaneously hypertensive rats (SHR) and normotensive Wistar Kyoto (WKY) controls. An additional aim was to assess the impact of vitamin D3 on DNA damage and oxidative stress markers. The gene expression profiles were determined by PCR array, DNA damage was assessed by an alkaline comet assay, and oxidative stress markers by measurement of thiobarbituric acid reactive substances (TBARS) and glutathione (GSH) levels. In SHR rats data showed that the groups of genes most differentially affected by supplemented and deficient diets were involved in BP regulation and renin-angiotensin system. In normotensive WKY controls, the profile of gene expression was similar between the two diets. SHR rats were more sensitive to changes in gene expression induced by dietary vitamin D3 than normotensive WKY animals. In addition to gene expression profile, vitamin D3 supplemented diet did not markedly affect DNA or levels of TBARS and GSH levels in both experimental groups. Vitamin D3 deficient diet produced lipid peroxidation in SHR rats. The results of this study contribute to a better understanding of the role of vitamin D3 in the genetic mechanisms underlying hypertension.

Abbreviations: AIN, American Institute of Nutrition; EDTA, disodium ethylenediaminetetraacetic acid; GSH, glutathione; PBS, phosphate buffer solution; SHR, spontaneously hypertensive rats; TBARS, thiobarbituric acid reactive substances; WKY, Wistar Kyoto.

KEYWORDS:

• Cholecalciferol
• gene expression
• hypertension
• SHR
• nutrigenomics

Acknowledgments

This study was supported by the São Paulo Research Foundation (FAPESP) and CAPES (Coordenação de Aperfeiçoamento de Pessoal de Ensino Superior). Carla da Silva Machado was sponsored by a fellowship from FAPESP, grant #2012/04325-9. The authors are grateful to Dr. Valdo José Dias da Silva (UFTM) for the donation of the SHR and WKY rats, to Regislaine Valeria Burin and Joana D`Arc Castania Darin for the laboratory assistance and to the Financier of Studies and Projects (FINEP, Brazil) for the acquisition of the StepOnePlus® system. LMGA thanks the fellowship of research productivity (PQ) granted by the National Council for Scientific and Technological Development (CNPq).

Conflict of interest statement

The authors declare that there are no conflicts of interest.

Additional information

Funding

This work was supported by the Fundação de Amparo à Pesquisa do Estado de São Paulo [#2012/04325-9].