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| Author(s): |
Carla da Silva Machado
Total Authors: 1
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| Document type: | Doctoral Thesis |
| Press: | Ribeirão Preto. |
| Institution: | Universidade de São Paulo (USP). Faculdade de Medicina de Ribeirão Preto (PCARP/BC) |
| Defense date: | 2016-02-17 |
| Examining board members: |
Lusania Maria Greggi Antunes;
Tiago Campos Pereira;
Mário Antonio Spanó;
Catarina Satie Takahashi
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| Advisor: | Lusania Maria Greggi Antunes |
| Abstract | |
Vitamin D3 is a micronutrient obtained from diet or by conversion of 7- dehydrocholesterol in the skin after exposure to UVB radiation. Vitamin D (D2 or D3) acts on the renin-angiotensin-aldosterone system, and its deficiency has been associated with hypertension development. This study aimed to evaluate the effect of vitamin D3 supplementation or deficiency in spontaneously hypertensive rats (SHR - spontaneously hypertensive rats) and their normotensive controls (Wistar Kyoto - WKY) on systolic blood pressure, DNA and chromosomes damage, biochemical markers of oxidative stress, oxidative burst in neutrophils, renal fibrosis and the gene expression profile of genes related to hypertension in kidney and heart. The rats were fed a vitamin D3 control diet (1,000 IU/kg) supplemented diet (10,000 IU/kg) or deficient diet (0 IU / kg) during 12 weeks. Vitamin D3 plasma quantification was performed by ELISA (Enzyme-Linked Immunosorbent Assay) technique and systolic blood pressure was measured weekly by noninvasive plethysmography of the caudal artery. DNA and chromosomal damage was evaluated by the comet assay in the peripheral blood, kidney and heart cells and by the micronucleus test in erythrocytes from bone marrow and peripheral blood; oxidative stress was evaluated by thiobarbituric acid reactive substances (TBARS) and glutathione (GHS) assays in kidney and heart; oxidative burst in neutrophils of peripheral blood; renal fibrosis by histology and gene expression by RT2 ProfilerTM PCR Arrays in kidney and heart. The results obtained for SHR rats showed that vitamin D3 supplementation reduced systolic blood pressure, did not induced DNA or chromosomal damage, oxidative stress or renal fibrosis, and regulated the expression of four genes involved with hypertension in the kidney (Ace, Agt, Ren and Edn1) and five genes in the heart (Ace, Avp, Ephx2, Mylk3 and Ren). Vitamin D3 deficiency increased systolic blood pressure, DNA damage in erythrocytes, lipid peroxidation in kidney and heart, oxidative burst in neutrophils and the renal fibrosis, and regulates the expression of thirteen genes involved with hypertension in kidney (Ace, Acta2, Agt, Agtr1a, Agtr1b, Alox5, Cacna1c, Ece1, Ednra, Kcnma1, P2rx4, Scnn1g and Slc7a1) and nine genes in heart (Ace, Agtr1b, Cacna1c, Drd5, Mylk2, Nostrin, Scnn1a, Scnn1g and Sphk1). In WKY rats, vitamin D3 supplementation altered the expression of Ren gene in the kidney and of ten genes in the heart (Ace2, Bdkrb2, Drd3, Drd5, Itpr1, Itpr2, Itpr3, Ptgs1, Scnn1a and Scnn1g); and vitamin D3 deficiency increased DNA damage in erythrocytes and renal fibrosis, and altered the expression of three genes in the kidney (Ace, Cps1 and Arg2) and six genes in the heart (Ace, Cacna, Ednra, Ephx2, Itpr1 and Itpr2). In the parameters systolic blood pressure, chromosomal damage, lipid peroxidation and oxidative burst, WKY rats fed with vitamin D3 supplemented or deficient diet did not differ compared to rats that received vitamin D3 control diet. In conclusion, the variation of dietary vitamin D3 levels altered the physiology of hypertension, acting as an antihypertensive in supplementation and aggravating the hypertension effects in its deficiency. (AU) | |
| FAPESP's process: | 12/04325-9 - "Evaluation of genomic instability, oxidative stress and modulation of gene expression by vitamin D in a model of spontaneously hypertensive rats" |
| Grantee: | Carla da Silva Machado |
| Support Opportunities: | Scholarships in Brazil - Doctorate |