Skip to main content
SpringerLink
Log in

Effect of Vitamin D on Endothelial Function and Blood Pressure

  • Chapter
  • First Online:
Cardio-Renal Clinical Challenges

Abstract

Chronic kidney disease (CKD) is associated with an increased rate of cardiovascular events [1], which is not fully explained by traditional risk factors and is increasingly associated with non-traditional risk factors [2]. Vitamin D deficiency is a non-traditional risk factor for cardiovascular events which becomes more relevant with declining renal function. At the same time, the deficiency of active vitamin D plays a major role in the mineral-bone disease of patients with CKD. The role of vitamin D deficiency in causing cardiovascular complications in the general population has attracted huge attention from researchers in recent years [3]. However, patients with kidney failure deserve further attention due to the role of kidneys in activating vitamin D.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
eBook
USD 16.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 159.00
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 109.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Go AS, Chertow GM, Fan D, McCulloch CE, Hsu CY. Chronic kidney disease and the risks of death, cardiovascular events, and hospitalization. N Engl J Med. 2004;351(13):1296–305.

    Article  CAS  PubMed  Google Scholar 

  2. Hajhosseiny R, Khavandi K, Goldsmith DJ. Cardiovascular disease in chronic kidney disease: untying the Gordian knot. Int J Clin Pract. 2013;67(1):14–31.

    Article  CAS  PubMed  Google Scholar 

  3. Wang TJ, Pencina MJ, Booth SL, Jacques PF, Ingelsson E, Lanier K, Benjamin EJ, D’Agostino RB, Wolf M, Vasan RS. Vitamin D deficiency and risk of cardiovascular disease. Circulation. 2008;117(4):503–11.

    Article  CAS  PubMed  Google Scholar 

  4. Fraser DR, Kodicek E. Unique biosynthesis by kidney of a biological active vitamin D metabolite. Nature. 1970;228(5273):764–6.

    Article  CAS  PubMed  Google Scholar 

  5. Kodicek E, Lawson DE, Wilson PW. Biological activity of a polar metabolite of vitamin D. Nature. 1970;228(5273):763–4.

    Article  CAS  PubMed  Google Scholar 

  6. Berl T, Berns AS, Hufer WE, Hammill K, Alfrey AC, Arnaud CD, Schrier RW. 1,25 dihydroxycholecalciferol effects in chronic dialysis. A double-blind controlled study. Ann Intern Med. 1978;88(6):774–80.

    Article  CAS  PubMed  Google Scholar 

  7. Palmer SC, McGregor DO, Craig JC, Elder G, Macaskill P, Strippoli GF. Vitamin D compounds for people with chronic kidney disease requiring dialysis. Cochrane Database Syst Rev. 2009;(4):CD005633.

    Google Scholar 

  8. Leckstroem DCT, Salzer J, Goldsmith DJA. The trials and tribulations of vitamin D: time for the ‘sunshine’ vitamin to come in out of the cold – or just more broken promises? Expert Rev Endocrinol Metab. 2014;9(4):327–44.

    Article  CAS  Google Scholar 

  9. Duranton F, Rodriguez-Ortiz ME, Duny Y, Rodriguez M, Daures JP, Argiles A. Vitamin D treatment and mortality in chronic kidney disease: a systematic review and meta-analysis. Am J Nephrol. 2013;37(3):239–48.

    Article  CAS  PubMed  Google Scholar 

  10. Kandula P, Dobre M, Schold JD, Schreiber Jr MJ, Mehrotra R, Navaneethan SD. Vitamin D supplementation in chronic kidney disease: a systematic review and meta-analysis of observational studies and randomized controlled trials. Clin J Am Soc Nephrol. 2011;6(1):50–62.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  11. Halcox JP, Donald AE, Ellins E, Witte DR, Shipley MJ, Brunner EJ, Marmot MG, Deanfield JE. Endothelial function predicts progression of carotid intima-media thickness. Circulation. 2009;119(7):1005–12.

    Article  PubMed  Google Scholar 

  12. Rossi R, Nuzzo A, Olaru AI, Origliani G, Modena MG. Endothelial function affects early carotid atherosclerosis progression in hypertensive postmenopausal women. J Hypertens. 2011;29(6):1136–44.

    Article  CAS  PubMed  Google Scholar 

  13. Yeboah J, Folsom AR, Burke GL, Johnson C, Polak JF, Post W, Lima JA, Crouse JR, Herrington DM. Predictive value of brachial flow-mediated dilation for incident cardiovascular events in a population-based study: the multi-ethnic study of atherosclerosis. Circulation. 2009;120(6):502–9.

    Article  PubMed Central  PubMed  Google Scholar 

  14. Rossi R, Nuzzo A, Origliani G, Modena MG. Prognostic role of flow-mediated dilation and cardiac risk factors in post-menopausal women. J Am Coll Cardiol. 2008;51(10):997–1002.

    Article  PubMed  Google Scholar 

  15. Recio-Mayoral A, Banerjee D, Streather C, Kaski JC. Endothelial dysfunction, inflammation and atherosclerosis in chronic kidney disease–a cross-sectional study of predialysis, dialysis and kidney-transplantation patients. Atherosclerosis. 2011;216(2):446–51.

    Article  CAS  PubMed  Google Scholar 

  16. Yilmaz MI, Stenvinkel P, Sonmez A, Saglam M, Yaman H, Kilic S, Eyileten T, Caglar K, Oguz Y, Vural A, Cakar M, Altun B, Yenicesu M, Carrero JJ. Vascular health, systemic inflammation and progressive reduction in kidney function; clinical determinants and impact on cardiovascular outcomes. Nephrol Dial Transplant. 2011;26(11):3537–43.

    Article  PubMed  Google Scholar 

  17. Flammer AJ, Anderson T, Celermajer DS, Creager MA, Deanfield J, Ganz P, Hamburg NM, Luscher TF, Shechter M, Taddei S, Vita JA, Lerman A. The assessment of endothelial function: from research into clinical practice. Circulation. 2012;126(6):753–67.

    Article  PubMed Central  PubMed  Google Scholar 

  18. Nanayakkara PW, van Guldener C, ter Wee PM, Scheffer PG, van Ittersum FJ, Twisk JW, Teerlink T, van Dorp W, Stehouwer CD. Effect of a treatment strategy consisting of pravastatin, vitamin E, and homocysteine lowering on carotid intima-media thickness, endothelial function, and renal function in patients with mild to moderate chronic kidney disease: results from the Anti-Oxidant Therapy in Chronic Renal Insufficiency (ATIC) Study. Arch Intern Med. 2007;167(12):1262–70.

    Article  CAS  PubMed  Google Scholar 

  19. Morimoto S, Maki K, Aota Y, Sakuma T, Iwasaka T. Beneficial effects of combination therapy with angiotensin II receptor blocker and angiotensin-converting enzyme inhibitor on vascular endothelial function. Hypertens Res. 2008;31(8):1603–10.

    Article  CAS  PubMed  Google Scholar 

  20. Chan DT, Watts GF, Irish AB, Dogra GK. Rosiglitazone does not improve vascular function in subjects with chronic kidney disease. Nephrol Dial Transplant. 2011;26(11):3543–9.

    Article  CAS  PubMed  Google Scholar 

  21. Cross JM, Donald AE, Nuttall SL, Deanfield JE, Woolfson RG, Macallister RJ. Vitamin C improves resistance but not conduit artery endothelial function in patients with chronic renal failure. Kidney Int. 2003;63(4):1433–42.

    Article  CAS  PubMed  Google Scholar 

  22. Baragetti I, Raselli S, Stucchi A, Terraneo V, Furiani S, Buzzi L, Garlaschelli K, Alberghini E, Catapano AL, Buccianti G. Improvement of endothelial function in uraemic patients on peritoneal dialysis: a possible role for 5-MTHF administration. Nephrol Dial Transplant. 2007;22(11):3292–7.

    Article  PubMed  Google Scholar 

  23. Caglar K, Yilmaz MI, Saglam M, Cakir E, Acikel C, Eyileten T, Yenicesu M, Oguz Y, Vural A, Carrero JJ, Axelsson J, Lindholm B, Stenvinkel P. Short-term treatment with sevelamer increases serum fetuin-a concentration and improves endothelial dysfunction in chronic kidney disease stage 4 patients. Clin J Am Soc Nephrol. 2008;3(1):61–8.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  24. Zheng H, Huang X, Zhang Q, Katz SD. Iron sucrose augments homocysteine-induced endothelial dysfunction in normal subjects. Kidney Int. 2006;69(4):679–84.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  25. Kassi E, Adamopoulos C, Basdra EK, Papavassiliou AG. Role of vitamin D in atherosclerosis. Circulation. 2013;128(23):2517–31.

    Article  PubMed  Google Scholar 

  26. Merke J, Milde P, Lewicka S, Hugel U, Klaus G, Mangelsdorf DJ, Haussler MR, Rauterberg EW, Ritz E. Identification and regulation of 1,25-dihydroxyvitamin D3 receptor activity and biosynthesis of 1,25-dihydroxyvitamin D3. Studies in cultured bovine aortic endothelial cells and human dermal capillaries. J Clin Invest. 1989;83(6):1903–15.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  27. Molinari C, Uberti F, Grossini E, Vacca G, Carda S, Invernizzi M, Cisari C. 1alpha,25-dihydroxycholecalciferol induces nitric oxide production in cultured endothelial cells. Cell Physiol Biochem. 2011;27(6):661–8.

    Article  CAS  PubMed  Google Scholar 

  28. Hirata M, Serizawa K, Aizawa K, Yogo K, Tashiro Y, Takeda S, Moriguchi Y, Endo K, Fukagawa M. 22-Oxacalcitriol prevents progression of endothelial dysfunction through antioxidative effects in rats with type 2 diabetes and early-stage nephropathy. Nephrol Dial Transplant. 2013;28(5):1166–74.

    Article  CAS  PubMed  Google Scholar 

  29. Equils O, Naiki Y, Shapiro AM, Michelsen K, Lu D, Adams J, Jordan S. 1,25-Dihydroxyvitamin D inhibits lipopolysaccharide-induced immune activation in human endothelial cells. Clin Exp Immunol. 2006;143(1):58–64.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  30. Talmor Y, Bernheim J, Klein O, Green J, Rashid G. Calcitriol blunts pro-atherosclerotic parameters through NFkappaB and p38 in vitro. Eur J Clin Invest. 2008;38(8):548–54.

    Article  CAS  PubMed  Google Scholar 

  31. 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(3):307–12.

    Article  CAS  PubMed  Google Scholar 

  32. 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(5):e36617.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  33. Witham MD, Adams F, Kabir G, Kennedy G, Belch JJ, Khan F. Effect of short-term vitamin D supplementation on markers of vascular health in South Asian women living in the UK–a randomised controlled trial. Atherosclerosis. 2013;230(2):293–9.

    Article  CAS  PubMed  Google Scholar 

  34. Witham MD, Dove FJ, Khan F, Lang CC, Belch JJ, Struthers AD. Effects of vitamin D supplementation on markers of vascular function after myocardial infarction–a randomised controlled trial. Int J Cardiol. 2013;167(3):745–9.

    Article  PubMed  Google Scholar 

  35. Witham MD, Price RJ, Struthers AD, Donnan PT, Messow CM, Ford I, McMurdo ME. Cholecalciferol treatment to reduce blood pressure in older patients with isolated systolic hypertension: the VitDISH randomized controlled trial. JAMA Intern Med. 2013;173(18):1672–9.

    CAS  PubMed  Google Scholar 

  36. Longenecker CT, Hileman CO, Carman TL, Ross AC, Seydafkan S, Brown TT, Labbato DE, Storer N, Tangpricha V, McComsey GA Vitamin D supplementation and endothelial function in vitamin D deficient HIV-infected patients: a randomized placebo-controlled trial. Antivir Ther. 2012;17(4):613–21.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  37. 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(10):2112–9.

    Article  CAS  PubMed  Google Scholar 

  38. Sokol SI, Srinivas V, Crandall JP, Kim M, Tellides G, Lebastchi AH, Yu Y, Gupta AK, Alderman MH. The effects of vitamin D repletion on endothelial function and inflammation in patients with coronary artery disease. Vas Med (London, England). 2012;17(6):394–404.

    Article  Google Scholar 

  39. 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(1):140–6.

    Article  CAS  PubMed  Google Scholar 

  40. 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 Metabol. 2009;94(10):4023–30.

    Article  CAS  Google Scholar 

  41. 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(5):557–62.

    Article  CAS  PubMed  Google Scholar 

  42. 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(10):864–70.

    Article  CAS  PubMed  Google Scholar 

  43. 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(3):320–5.

    Article  CAS  PubMed  Google Scholar 

  44. Dreyer G, Tucker AT, Harwood SM, Pearse RM, Raftery MJ, Yaqoob MM. Ergocalciferol and microcirculatory function in chronic kidney disease and concomitant vitamin D deficiency: an exploratory, double blind. Randomised controlled trial. PLOS One. 2014;9(7):e99461.

    Article  PubMed Central  PubMed  Google Scholar 

  45. London GM, Guerin AP, Verbeke FH, Pannier B, Boutouyrie P, Marchais SJ, Metivier F. Mineral metabolism and arterial functions in end-stage renal disease: potential role of 25-hydroxyvitamin D deficiency. J Am Soc Nephrol. 2007;18(2):613–20.

    Article  CAS  PubMed  Google Scholar 

  46. Chitalia N, Recio-Mayoral A, Kaski JC, Banerjee D. Vitamin D deficiency and endothelial dysfunction in non-dialysis chronic kidney disease patients. Atherosclerosis. 2012;220(1):265–8.

    Article  CAS  PubMed  Google Scholar 

  47. Alborzi P, Patel NA, Peterson C, Bills JE, Bekele DM, Bunaye Z, Light RP, Agarwal R. Paricalcitol reduces albuminuria and inflammation in chronic kidney disease: a randomized double-blind pilot trial. Hypertension. 2008;52(2):249–55.

    Article  CAS  PubMed  Google Scholar 

  48. Chitalia N, Ismail T, Tooth L, Boa F, Hampson G, Goldsmith D, Kaski JC, Banerjee D. Impact of vitamin d supplementation on arterial vasomotion, stiffness and endothelial biomarkers in chronic kidney disease patients. PLoS One. 2014;9(3):e91363.

    Article  PubMed Central  PubMed  Google Scholar 

  49. Carrara D, Bernini M, Bacca A, Rugani I, Duranti E, Virdis A, Ghiadoni L, Taddei S, Bernini G. Cholecalciferol administration blunts the systemic renin-angiotensin system in essential hypertensives with hypovitaminosis D. J Renin Angiotensin Aldosterone Syst. 2014;15(1):82–7.

    Article  CAS  PubMed  Google Scholar 

  50. 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(41):29821–30.

    Article  CAS  PubMed  Google Scholar 

  51. Beveridge LA, Witham MD. Vitamin D and the cardiovascular system. Osteoporos Int. 2013;24(8):2167–80.

    Article  CAS  PubMed  Google Scholar 

  52. Burgaz A, Orsini N, Larsson SC, Wolk A. Blood 25-hydroxyvitamin D concentration and hypertension: a meta-analysis. J Hypertens. 2011;29(4):636–45.

    Article  CAS  PubMed  Google Scholar 

  53. Forman JP, Scott JB, Ng K, Drake BF, Suarez EG, Hayden DL, Bennett GG, Chandler PD, Hollis BW, Emmons KM, Giovannucci EL, Fuchs CS, Chan AT. Effect of vitamin D supplementation on blood pressure in blacks. Hypertension. 2013;61(4):779–85.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  54. 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(5):307–14.

    Article  PubMed Central  PubMed  Google Scholar 

  55. Molina P, Gorriz JL, Molina MD, Peris A, Beltran S, Kanter J, Escudero V, Romero R, Pallardo LM. The effect of cholecalciferol for lowering albuminuria in chronic kidney disease: a prospective controlled study. Nephrol Dial Transplant. 2014;29(1):97–109.

    Article  CAS  PubMed  Google Scholar 

  56. Alvarez JA, Law J, Coakley KE, Zughaier SM, Hao L, Shahid Salles K, Wasse H, Gutierrez OM, Ziegler TR, Tangpricha V. High-dose cholecalciferol reduces parathyroid hormone in patients with early chronic kidney disease: a pilot, randomized, double-blind, placebo-controlled trial. Am J Clin Nutr. 2012;96(3):672–9.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  57. Marckmann P, Agerskov H, Thineshkumar S, Bladbjerg EM, Sidelmann JJ, Jespersen J, Nybo M, Rasmussen LM, Hansen D, Scholze A. Randomized controlled trial of cholecalciferol supplementation in chronic kidney disease patients with hypovitaminosis D. Nephrol Dial Transplant. 2012;27(9):3523–31.

    Article  CAS  PubMed  Google Scholar 

  58. Bolland MJ, Grey A, Gamble GD, Reid IR. The effect of vitamin D supplementation on skeletal, vascular, or cancer outcomes: a trial sequential meta-analysis. Lancet Diabetes Endocrinol. 2014;2(4):307–20.

    Article  CAS  PubMed  Google Scholar 

  59. Sanders KM, Stuart AL, Williamson EJ, Simpson JA, Kotowicz MA, Young D, Nicholson GC. Annual high-dose oral vitamin D and falls and fractures in older women: a randomized controlled trial. JAMA. 2010;303(18):1815–22.

    Article  CAS  PubMed  Google Scholar 

  60. Powe CE, Evans MK, Wenger J, Zonderman AB, Berg AH, Nalls M, Tamez H, Zhang D, Bhan I, Karumanchi SA, Powe NR, Thadhani R. Vitamin D-binding protein and vitamin D status of black Americans and white Americans. N Engl J Med. 2013;369(21):1991–2000.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  61. Wilkinson RJ, Llewelyn M, Toossi Z, Patel P, Pasvol G, Lalvani A, Wright D, Latif M, Davidson RN. Influence of vitamin D deficiency and vitamin D receptor polymorphisms on tuberculosis among Gujarati Asians in west London: a case-control study. Lancet. 2000;355(9204):618–21.

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgement

We wish to thank Somaeih Siroussarjou, Riya Banerjee and David Oliveira for their help with manuscript preparation

Author information

Authors and Affiliations

  1. Renal and Transplantation Unit, St George’s Healthcare NHS Trust, Knightsbridge Wing, Blackshaw Road, Tooting, London, SW17 0QT, UK

    Debasish Banerjee MBBS, MD, FRCP

  2. Department of Nephrology and Transplantation, Guy’s Hospitals, Great Maze Pond, London, SE1 9RT, UK

    David Goldsmith (Professor of Cardiorenal Medicine)

Authors
  1. Debasish Banerjee MBBS, MD, FRCP
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. David Goldsmith
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Debasish Banerjee MBBS, MD, FRCP .

Editor information

Editors and Affiliations

  1. Renal and Transplantation Department, Guy's Hospital, London, United Kingdom

    David Goldsmith

  2. Gr. T. Popa University of Medicine and Pharmacy, Iasi, Romania

    Adrian Covic

  3. Karolinska Institutet Danderyd University Hospital, Stockholm, Sweden

    Jonas Spaak

Rights and permissions

Reprints and permissions

Copyright information

© 2015 Springer International Publishing Switzerland

About this chapter

Cite this chapter

Banerjee, D., Goldsmith, D. (2015). Effect of Vitamin D on Endothelial Function and Blood Pressure. In: Goldsmith, D., Covic, A., Spaak, J. (eds) Cardio-Renal Clinical Challenges. Springer, Cham. https://doi.org/10.1007/978-3-319-09162-4_10

Download citation

  • DOI: https://doi.org/10.1007/978-3-319-09162-4_10

  • Published:

  • Publisher Name: Springer, Cham

  • Print ISBN: 978-3-319-09161-7

  • Online ISBN: 978-3-319-09162-4

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics

Search

Navigation