The renin-angiotensin system (RAS) plays a central role in the regulation of blood pressure, volume and electrolyte homeostasis. Inappropriate activation of the RAS may lead to hypertension. Clinical and epidemiological studies have suggested a correlation between Vitamin D-deficiency and high blood pressure. Our recent studies demonstrate that Vitamin D is a potent endocrine suppressor of renin biosynthesis to regulate the RAS. Mice lacking the Vitamin D receptor (VDR) have elevated production of renin and angiotensin (Ang) II, leading to hypertension, cardiac hypertrophy and increased water intake. These abnormalities can be prevented by treatment with an ACE inhibitor or AT(1) receptor antagonist. Vitamin D repression of renin expression is independent of calcium metabolism, the volume- and salt-sensing mechanisms and the Ang II feedback regulation. In normal mice, Vitamin D-deficiency stimulates renin expression, whereas injection of 1,25-dihydroxyvitamin D(3) [1,25(OH)(2)D(3)] reduces renin synthesis. In cell cultures, 1,25(OH)(2)D(3) directly suppresses renin gene transcription by a VDR-dependent mechanism. Furthermore, we have found that Gemini compounds have more potent renin-suppressing activity than 1,25(OH)(2)D(3). Collectively, our studies reveal a critical role of the Vitamin D endocrine system in the regulation of blood pressure and volume homeostasis, and suggest that low calcemic Vitamin D analogs may potentially be developed into a new class of anti-hypertensive agents to control renin production and blood pressure.
Vitamin D deficiency is a major public health problem worldwide in all age groups, even in those residing in countries with low latitude, where it was generally assumed that UV radiation was adequate enough to prevent this deficiency, and in industrialized countries, where vitamin D fortification has been implemented now for years. However, most countries are still lacking data, particularly population representative data, with very limited information in infants, children, adolescents and pregnant women. Since the number of recent publications is escalating, with a broadening of the geographic diversity, the objective of the present report was to conduct a more recent systematic review of global vitamin D status, with particular emphasis in at risk groups. A systematic review was conducted in PubMed/Medline in April-June 2013 to identify articles on vitamin D status worldwide published in the last 10 years in apparently healthy individuals. Only studies with vitamin D status prevalence were included. If available, the first source selected was population-based or representative samples studies. Clinical trials, case-control studies, case reports or series, reviews, validation studies, letters, editorials, or qualitative studies were excluded. A total of 103 articles were eligible and included in the present report. Maps were created for each age group, providing an updated overview of global vitamin D status. In areas with available data, the prevalence of low vitamin D status is a global problem in all age groups, in particular in girls and women from the Middle East. These maps also evidenced the regions with missing data for each specific population groups. There is striking lack of data in infants, children and adolescents worldwide, and in most countries of South America and Africa. In conclusion, vitamin D deficiency is a global public health problem in all age groups, particularly in those from the Middle East. This article is part of a Special Issue entitled '16th Vitamin D Workshop'.