Effects of vitamin d on blood pressure and endothelial function

Bokyung Min, Bokyung Min

Abstract

Vitamin D deficiency is prevalent, primarily due to limited sun exposure, which may be observed in urban areas, or as a result of modern lifestyles. Common myths about vitamin D persist, including that it is mostly obtained from the diet and is only essential for bone and mineral homeostasis. Nonetheless, advances in biomedical science suggest that vitamin D is a hormone that is integral to numerous physiologic functions in most cells and tissues. Therefore, abnormal vitamin D levels may contribute to health disturbances. A number of recent reports on potential associations between vitamin D deficiency and cardiovascular disease have highlighted its role in this system. A focus over the previous decade has been to better understand the mechanisms behind vitamin D regulation and the pathophysiology associated with suboptimal vitamin D levels. Vitamin D deficiency is highly associated with the incidence of cardiovascular diseases, even when considering other well-known risk factors. In this process, the renin-angiotensin system is disrupted, and hypertension and endothelial dysfunction contribute to the risk of cardiovascular disease. Likewise, clinical outcomes upon the normalization of vitamin D levels have been investigated in different patient populations. It makes sense that vitamin D supplementation to improve vitamin D status among vitamin D-deficient individuals could be useful without requiring a sudden lifestyle change. This manuscript provides a brief overview of vitamin D metabolism and the vitamin D receptor. It also summarizes the current clinical research relating to vitamin D supplementation and its effects on hypertension and endothelial dysfunction in cardiovascular medicine.

Keywords: 25-hydroxyvitamin D; Blood pressure; Calcitriol; Endothelial dysfunction; Vitamin D.

Figures

Fig. 1
Fig. 1
Interactions between vitamin D receptor and retinoid X receptors inducing vitamin D response elements. Adapted from reference .
Fig. 2
Fig. 2
A proposed mechanism of 1,25-dihydroxyvitamin D3 on reninexpression [Adapted from reference 28].

References

    1. DeLuca HF. Overview of general physiologic features and functions of vitamin D. Am J Clin Nutr. 2004;80(6 Suppl):1689S–1696S.
    1. Bouillon R, Carmeliet G, Verlinden L, van Etten E, Verstuyf A, Luderer HF, Lieben L, Mathieu C, Demay M. Vitamin D and human health: lessons from vitamin D receptor null mice. Endocr Rev. 2008;29:726–776.
    1. Ferder M, Inserra F, Manucha W, Ferder L. The world pandemic of vitamin D deficiency could possibly be explained by cellular inflammatory response activity induced by the renin-angiotensin system. Am J Physiol Cell Physiol. 2013;304:C1027–C1039.
    1. Kim DH, Sabour S, Sagar UN, Adams S, Whellan DJ. Prevalence of hypovitaminosis D in cardiovascular diseases (from the National Health and Nutrition Examination Survey 2001 to 2004) Am J Cardiol. 2008;102:1540–1544.
    1. Holick MF. Vitamin D deficiency. N Engl J Med. 2007;357:266–281.
    1. Kamen DL, Tangpricha V. Vitamin D and molecular actions on the immune system: modulation of innate and autoimmunity. J Mol Med (Berl) 2010;88:441–450.
    1. Suzuki Y, Ichiyama T, Ohsaki A, Hasegawa S, Shiraishi M, Furukawa S. Anti-inflammatory effect of 1alpha,25-dihydroxyvitamin D(3) in human coronary arterial endothelial cells: Implication for the treatment of Kawasaki disease. J Steroid Biochem Mol Biol. 2009;113:134–138.
    1. Wong MS, Delansorne R, Man RY, Vanhoutte PM. Vitamin D derivatives acutely reduce endothelium-dependent contractions in the aorta of the spontaneously hypertensive rat. Am J Physiol Heart Circ Physiol. 2008;295:H289–H296.
    1. Holick MF, Binkley NC, Bischoff-Ferrari HA, Gordon CM, Hanley DA, Heaney RP, Murad MH, Weaver CM Endocrine Society. Evaluation, treatment, and prevention of vitamin D deficiency: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab. 2011;96:1911–1930.
    1. Cheng JB, Motola DL, Mangelsdorf DJ, Russell DW. De-orphanization of cytochrome P450 2R1: a microsomal vitamin D 25-hydroxilase. J Biol Chem. 2003;278:38084–38093.
    1. Pera Ł, Sygitowicz G, Białek S, Łukaszkiewicz J, Sitkiewicz D. Vitamin D and statins: action in preventing cardiovascular events. Kardiol Pol. 2012;70:1296–1298.
    1. Yavuz B, Ertugrul DT, Cil H, Ata N, Akin KO, Yalcin AA, Kucukazman M, Dal K, Hokkaomeroglu MS, Yavuz BB, Tutal E. Increased levels of 25 hydroxyvitamin D and 1,25-dihydroxyvitamin D after rosuvastatin treatment: a novel pleiotropic effect of statins? Cardiovasc Drugs Ther. 2009;23:295–299.
    1. Schwartz JB. Effects of vitamin D supplementation in atorvastatin-treated patients: a new drug interaction with an unexpected consequence. Clin Pharmacol Ther. 2009;85:198–203.
    1. Brewer LC, Michos ED, Reis JP. Vitamin D in atherosclerosis, vascular disease, and endothelial function. Curr Drug Targets. 2011;12:54–60.
    1. Brandenburg VM, Vervloet MG, Marx N. The role of vitamin D in cardiovascular disease: from present evidence to future perspectives. Atherosclerosis. 2012;225:253–263.
    1. Nibbelink KA, Tishkoff DX, Hershey SD, Rahman A, Simpson RU. 1,25(OH)2-vitamin D3 actions on cell proliferation, size, gene expression, and receptor localization, in the HL-1 cardiac myocyte. J Steroid Biochem Mol Biol. 2007;103:533–537.
    1. Koszewski NJ, Herberth J, Malluche HH. Retinoic acid receptor gamma 2 interactions with vitamin D response elements. J Steroid Biochem Mol Biol. 2010;120:200–207.
    1. Al Mheid I, Patel RS, Tangpricha V, Quyyumi AA. Vitamin D and cardiovascular disease: is the evidence solid? Eur Heart J. 2013 [Epub ahead of print]
    1. Yang L, Ma J, Zhang X, Fan Y, Wang L. Protective role of the vitamin D receptor. Cell Immunol. 2012;279:160–166.
    1. Haussler MR, Jurutka PW, Mizwicki M, Norman AW. Vitamin D receptor (VDR)-mediated actions of 1α,25(OH)2 vitamin D3: genomic and non-genomic mechanisms. Best Pract Res Clin Endocrinol Metab. 2011;25:543–559.
    1. Swapna N, Vamsi UM, Usha G, Padma T. Risk conferred by FokI polymorphism of vitamin D receptor (VDR) gene for essential hypertension. Indian J Hum Genet. 2011;17:201–206.
    1. Kammerer CM, Dualan AA, Samollow PB, Périssé AR, Bauer RL, MacCluer JW, O'Leary DH, Mitchell BD. Bone mineral density, carotid artery intimal medial thickness, and the vitamin D receptor BsmI polymorphism in Mexican American women. Calcif Tissue Int. 2004;75:292–298.
    1. Abd El Gawad SS, Abdul Samee ER, Metwali AA, Abd El Gawad MS. Vitamin D receptor gene polymorphism and its association with 1,25-dihydroxyvitamin D3 in patients with Graves disease in an Egyptian population: a pilot study. Endocr Pract. 2012;18:132–139.
    1. Györffy B, Vásárhelyi B, Krikovszky D, Madácsy L, Tordai A, Tulassay T, Szabó A. Gender-specific association of vitamin D receptor polymorphism combinations with type 1 diabetes mellitus. Eur J Endocrinol. 2002;147:803–808.
    1. Seals DR, Jablonski KL, Donato AJ. Aging and vascular endothelial function in humans. Clin Sci (Lond) 2011;120:357–375.
    1. Deanfield J, Donald A, Ferri C, Giannattasio C, Halcox J, Halligan S, Lerman A, Mancia G, Oliver JJ, Pessina AC, Rizzoni D, Rossi GP, Salvetti A, Schiffrin EL, Taddei S, Webb DJ Working Group on Endothelin and Endothelial Factors of the European Society of Hypertension. Endothelial function and dysfunction. Part I: Methodological issues for assessment in the different vascular beds: a statement by the Working Group on Endothelin and Endothelial Factors of the European Society of Hypertension. J Hypertens. 2005;23:7–17.
    1. Csiszar A, Smith KE, Koller A, Kaley G, Edwards JG, Ungvari Z. Regulation of bone morphogenetic protein-2 expression in endothelial cells: role of nuclear factor-kappaB activation by tumor necrosis factor-alpha, H2O2, and high intravascular pressure. Circulation. 2005;111:2364–2372.
    1. Zhou C, Lu F, Cao K, Xu D, Goltzman D, Miao D. Calcium-independent and 1,25(OH)2D3-dependent regulation of the renin-angiotensin system in 1alpha-hydroxylase knockout mice. Kidney Int. 2008;74:170–179.
    1. Resnick LM, Müller FB, Laragh JH. Calcium-regulating hormones in essential hypertension. Relation to plasma renin activity and sodium metabolism. Ann Intern Med. 1986;105:649–654.
    1. Li YC, Kong J, Wei M, Chen ZF, Liu SQ, Cao LP. 1,25-Dihydroxyvitamin D(3) is a negative endocrine regulator of the renin-angiotensin system. J Clin Invest. 2002;110:229–238.
    1. Xiang W, Kong J, Chen S, Cao LP, Qiao G, Zheng W, Liu W, Li X, Gardner DG, Li YC. Cardiac hypertrophy in vitamin D receptor knockout mice: role of the systemic and cardiac reninangiotensin systems. Am J Physiol Endocrinol Metab. 2005;288:E125–E132.
    1. Yuan W, Pan W, Kong J, Zheng W, Szeto FL, Wong KE, Cohen R, Klopot A, Zhang Z, Li YC. 1,25-dihydroxyvitamin D3 suppresses renin gene transcription by blocking the activity of the cyclic AMP response element in the renin gene promoter. J Biol Chem. 2007;282:29821–29830.
    1. Tedgui A, Mallat Z. Cytokines in atherosclerosis: pathogenic and regulatory pathways. Physiol Rev. 2006;86:515–581.
    1. Ginde AA, Liu MC, Camargo CA., Jr Demographic differences and trends of vitamin D insufficiency in the US population, 1988-2004. Arch Intern Med. 2009;169:626–632.
    1. Melamed ML, Michos ED, Post W, Astor B. 25-hydroxyvitamin D levels and the risk of mortality in the general population. Arch Intern Med. 2008;168:1629–1637.
    1. Scragg R, Sowers M, Bell C. Serum 25-hydroxyvitamin D, ethnicity, and blood pressure in the Third National Health and Nutrition Examination Survey. Am J Hypertens. 2007;20:713–719.
    1. Forman JP, Giovannucci E, Holmes MD, Bischoff-Ferrari HA, Tworoger SS, Willett WC, Curhan GC. Plasma 25-hydroxyvitamin D levels and risk of incident hypertension. Hypertension. 2007;49:1063–1069.
    1. Pfeifer M, Begerow B, Minne HW, Nachtigall D, Hansen C. Effects of a short-term vitamin D(3) and calcium supplementation on blood pressure and parathyroid hormone levels in elderly women. J Clin Endocrinol Metab. 2001;86:1633–1637.
    1. Dong Y, Stallmann-Jorgensen IS, Pollock NK, Harris RA, Keeton D, Huang Y, Li K, Bassali R, Guo DH, Thomas J, Pierce GL, White J, Holick MF, Zhu H. A 16-week randomized clinical trial of 2000 international units daily vitamin D3 supplementation in black youth: 25-hydroxyvitamin D, adiposity, and arterial stiffness. J Clin Endocrinol Metab. 2010;95:4584–4591.
    1. Witham MD, Nadir MA, Struthers AD. Effect of vitamin D on blood pressure: a systematic review and meta-analysis. J Hypertens. 2009;27:1948–1954.
    1. Pittas AG, Chung M, Trikalinos T, Mitri J, Brendel M, Patel K, Lichtenstein AH, Lau J, Balk EM. Systematic review: Vitamin D and cardiometabolic outcomes. Ann Intern Med. 2010;152:307–314.
    1. Wu SH, Ho SC, Zhong L. Effects of vitamin D supplementation on blood pressure. South Med J. 2010;103:729–737.
    1. Elamin MB, Abu Elnour NO, Elamin KB, Fatourechi MM, Alkatib AA, Almandoz JP, Liu H, Lane MA, Mullan RJ, Hazem A, Erwin PJ, Hensrud DD, Murad MH, Montori VM. Vitamin D and cardiovascular outcomes: a systematic review and meta-analysis. J Clin Endocrinol Metab. 2011;96:1931–1942.
    1. Sugden JA, Davies JI, Witham MD, Morris AD, Struthers AD. Vitamin D improves endothelial function in patients with Type 2 diabetes mellitus and low vitamin D levels. Diabet Med. 2008;25:320–325.
    1. Tarcin O, Yavuz DG, Ozben B, Telli A, Ogunc AV, Yuksel M, Toprak A, Yazici D, Sancak S, Deyneli O, Akalin S. Effect of vitamin D deficiency and replacement on endothelial function in asymptomatic subjects. J Clin Endocrinol Metab. 2009;94:4023–4030.
    1. Yiu YF, Yiu KH, Siu CW, Chan YH, Li SW, Wong LY, Lee SW, Tam S, Wong EW, Lau CP, Cheung BM, Tse HF. Randomized controlled trial of vitamin D supplement on endothelial function in patients with type 2 diabetes. Atherosclerosis. 2013;227:140–146.
    1. Harris RA, Pedersen-White J, Guo DH, Stallmann-Jorgensen IS, Keeton D, Huang Y, Shah Y, Zhu H, Dong Y. Vitamin D3 supplementation for 16 weeks improves flow-mediated dilation in overweight African-American adults. Am J Hypertens. 2011;24:557–562.
    1. Stricker H, Tosi Bianda F, Guidicelli-Nicolosi S, Limoni C, Colucci G. Effect of a single, oral, high-dose vitamin D supplementation on endothelial function in patients with peripheral arterial disease: a randomised controlled pilot study. Eur J Vasc Endovasc Surg. 2012;44:307–312.
    1. Witham MD, Dove FJ, Dryburgh M, Sugden JA, Morris AD, Struthers AD. The effect of different doses of vitamin D(3) on markers of vascular health in patients with type 2 diabetes: a randomised controlled trial. Diabetologia. 2010;53:2112–2119.
    1. Witham MD, Dove FJ, Sugden JA, Doney AS, Struthers AD. The effect of vitamin D replacement on markers of vascular health in stroke patients - a randomised controlled trial. Nutr Metab Cardiovasc Dis. 2012;22:864–870.
    1. Gepner AD, Ramamurthy R, Krueger DC, Korcarz CE, Binkley N, Stein JH. A prospective randomized controlled trial of the effects of vitamin D supplementation on cardiovascular disease risk. PLoS One. 2012;7:e36617.
    1. Effects of Vitamin D and Omega-3 Fatty Acids on Infectious Diseases and hCAP18. [Accessed on Jun 23, 2013]. Available at .
    1. Vitamin D Supplementation and Metabolism in Vitamin D Deficient Elderly (VitD) [Accessed on Jun 23, 2013]. Available at .

Source: PubMed

Sponsorer och medarbetare

Medicinska tillstånd

Läkemedelsinterventioner

3
Prenumerera