Latest Knowledge on the Role of Vitamin D in Hypertension

Abstract

Hypertension is the third leading cause of the global disease burden, and while populations live longer, adopt more sedentary lifestyles, and become less economically concerned, the prevalence of hypertension is expected to increase. Pathologically elevated blood pressure (BP) is the strongest risk factor for cardiovascular disease (CVD) and related disability, thus making it imperative to treat this disease. Effective standard pharmacological treatments, i.e., diuretics, angiotensin converting enzyme (ACE) inhibitors, angiotensin receptor blocker (ARBs), beta-adrenergic receptor blockers (BARBs), and calcium channel blockers (CCBs), are available. Vitamin D (vitD) is known best for its role in bone and mineral homeostasis. Studies with vitamin D receptor (VDR) knockout mice show an increased renin-angiotensin-aldosterone system (RAAS) activity and increased hypertension, suggesting a key role for vitD as a potential antihypertensive agent. Similar studies in humans displayed ambiguous and mixed results. No direct antihypertensive effect was shown, nor a significant impact on the human RAAS. Interestingly, human studies supplementing vitD with other antihypertensive agents reported more promising results. VitD is considered a safe supplement, proposing its great potential as antihypertensive supplement. The aim of this review is to examine the current knowledge about vitD and its role in the treatment of hypertension.

Keywords: antihypertensive treatment; clinical trials; hypertension; molecular mechanisms; supplement; vitamin D; vitamin D deficiency.

Figure 1

Illustrated abstract of Vitamin D and its role in hypertension. This figure was made using Biorender.com, agreement number MD24V0MZH0.

Figure 2

Flow diagram of the literature searched for this review. (Made with https://estech.shinyapps.io/prisma_flowdiagram/, accessed on 11 December 2022).

Figure 3

1,25(OH)₂D₃ genomic (1) and non-genomic (2) pathways. The VDR acts with other nuclear hormone receptors, especially the RXR [47]. 1,25(OH)₂D₃ crosses the cell membrane and enters the nucleus, where it interacts with the VDR. The VDR/1,25(OH)₂D complex translocates into the nucleus in a ligand-dependent fashion [48]. In the nucleus, the VDR/1,25(OH)₂D generates an active signal transduction complex consisting of the heterodimer of the vitamin D-liganded VDR and the RXR. The VDR/RXR heterodimer recognizes the HRE in the DNA sequence of the vitamin D-regulated genes [46]. Here, regulation of gene expression in specific tissues mediated by the VDR occurs, evoking the (1) genomic response. (2) The non-genomic actions are mediated by binding of calcitriol to the membrane located 1,25-D-MARRS, which affects numerous intracellular cell signaling pathways modulating the effects of gene expression through signal transduction to target transcription factors SP1, SP3, and RXR [51,52]. This figure was made using Biorender.com, agreement number XE24V0N4B7.

Figure 4

Effects of vitamin D and its metabolites in calcium homeostasis, bone metabolism, and the immune system. Vitamin D₃ obtained from the diet or synthesized by photoconversion from sunlight is converted into the hormonal form 1,25(OH)₂D₃ by two hydroxylations occurring in the liver and kidney, respectively. After this conversion, 1,25(OH)₂D₃ circulates in blood to target tissues. The integrated actions of the 1,25(OH)₂D₃ hormone via binding to the intracellular VDR, to control calcium homeostasis in bone, kidney, intestine, and parathyroid, is shown above [64]. This figure was made using Biorender.com, agreement number UN24V0NHC0.