Vitamin D Deficiency-induced Hypertension Is Associated With Vascular Oxidative Stress and Altered Heart Gene Expression

Abstract

Vitamin D deficiency (VDD) is associated with an increased cardiovascular risk. We investigated the effect of VDD on the cardiovascular system of growing male rats fed with a vitamin D-deficient diet. Using isolated rat aorta, we assessed both superoxide anion and endothelial-dependent relaxations. Microarray technology was used to identify changes induced by VDD in cardiac gene expression. Compared with control, VDD increased systolic blood pressure (P < 0.05) and superoxide anion production in the aortic wall (P < 0.05) and tended to increase serum levels of angiotensin II and atrial natriuretic peptide (P < 0.15). However, VDD slightly improved maximal relaxation to acetylcholine from 75 % ± 3% to 83% ± 2% (P < 0.05). Incubation of aortic rings either with nitro-l-arginine methyl ester (l-NAME) or catalase did not eliminate the enhancement of endothelial-mediated relaxation observed in vitamin D-deficient rats. Only incubation with indometacin or calcium-activated potassium channels blockers suppressed this difference. Compared with control, the expression of 51 genes showed different expression, including several genes involved in the regulation of oxidative stress and myocardial hypertrophy. In conclusion, VDD in early life increases arterial blood pressure, promotes vascular oxidative stress, and induces changes in cardiac gene expression. However, the endothelial-mediated regulation of vasomotor tone is maintained throughout the enhancement of an NO-independent compensatory pathway.

Impact of the Length of Vitamin D Deficiency on Cardiac Remodeling

“…39 VDD was related to higher vascular oxidative stress. 33 In the present study, VDD was associated not only with increased reactive oxygen species in the cardiac tissue, as shown by the higher lipid hydroperoxide, but also with reduced activity of catalase and glutathione peroxidase. It is important to consider a possible mechanism to compensate the increased oxidative stress that occurs through the Nrf-2 pathway.…”

“…Therefore, some studies have shown that VDD can influence energetic metabolism, 29 inflammation, [30][31][32] and oxidative stress. 33 These changes are part of the cardiac remodeling process.…”

Nanomedical studies of the restoration of nitric oxide/peroxynitrite balance in dysfunctional endothelium by 1,25-dihydroxy vitamin D₃ &ndash; clinical implications for cardiovascular diseases

“…Our study provides direct molecular insight to previously published observations that have suggested that vitamin D 3 deficiency-induced hypertension is associated with vascular oxidative stress. 29 It is well documented that oxidative stress is involved in vascular complications and development of hypertension. 30 Oxidative and nitroxidative stress impairs endothelium-dependent relaxation of the blood vessels and is involved in the facilitation of smooth muscles contractions.…”

“…29 However, none of these studies provided any direct proof of how vitamin D 3 improves NO production and decreases nitroxidative stress. Our studies are not only coherent with previous observations, but provide new direct evidence, on the molecular level, why vitamin D 3 can be highly beneficial for the treatment of a dysfunctional cardiovascular system.…”

A deficiência de vitamina D é um potencial fator de risco para nefrotoxicidade induzida por contraste

“…Several studies report a linkage between VDD and up-regulation of RAS, oxidative stress and endothelial dysfunction (3,10,20,28). By means of flow mediated dilation and serum TBARS in asymptomatic subjects, Tarcin et al have shown that VDD is associated with endothelial dysfunction and increased lipid peroxidation (27).…”