Vitamin D depletion aggravates hypertension and target-organ damage

J Am Heart Assoc. 2015 Jan 28;4(2):e001417. doi: 10.1161/JAHA.114.001417.


Background: We tested the controversial hypothesis that vitamin D depletion aggravates hypertension and target-organ damage by influencing renin.

Methods and results: Four-week-old double-transgenic rats (dTGR) with excess angiotensin (Ang) II production due to overexpression of the human renin (hREN) and angiotensinogen (hAGT) genes received vitamin D-depleted (n=18) or standard chow (n=15) for 3 weeks. The depleted group had very low serum 25-hydroxyvitamin D levels (mean±SEM; 3.8±0.29 versus 40.6±1.19 nmol/L) and had higher mean systolic BP at week 5 (158±3.5 versus 134.6±3.7 mm Hg, P<0.001), week 6 (176.6±3.3 versus 162.3±3.8 mm Hg, P<0.01), and week 7 (171.6±5.1 versus 155.9±4.3 mm Hg, P<0.05). Vitamin D depletion led to increased relative heart weights and increased serum creatinine concentrations. Furthermore, the mRNAs of natriuretic peptides, neutrophil gelatinase-associated lipocalin, hREN, and rRen were increased by vitamin D depletion. Regulatory T cells in the spleen and in the circulation were not affected. Ang metabolites, including Ang II and the counter-regulatory breakdown product Ang 1 to 7, were significantly up-regulated in the vitamin D-depleted groups, while ACE-1 and ACE-2 activities were not affected.

Conclusions: Short-term severe vitamin D depletion aggravated hypertension and target-organ damage in dTGR. Our data suggest that even short-term severe vitamin D deficiency may directly promote hypertension and impacts on renin-angiotensin system components that could contribute to target-organ damage. The findings add to the evidence that vitamin D deficiency could also affect human hypertension.

Keywords: hypertension; renin; vitamin D.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acute-Phase Proteins / genetics
  • Angiotensin II / genetics
  • Angiotensinogen / genetics
  • Animals
  • Blood Pressure / genetics
  • Creatinine / blood
  • Heart / physiopathology*
  • Humans
  • Hypertension / etiology*
  • Hypertension / metabolism*
  • Lipocalin-2
  • Lipocalins / genetics
  • Natriuretic Peptides / genetics
  • Proto-Oncogene Proteins / genetics
  • RNA, Messenger
  • Rats
  • Rats, Sprague-Dawley
  • Rats, Transgenic
  • Renin / genetics
  • Renin-Angiotensin System / genetics*
  • Risk Factors
  • Vitamin D / analogs & derivatives
  • Vitamin D / blood
  • Vitamin D / metabolism*
  • Vitamin D Deficiency / complications*
  • Vitamin D Deficiency / etiology


  • Acute-Phase Proteins
  • Lcn2 protein, rat
  • Lipocalin-2
  • Lipocalins
  • Natriuretic Peptides
  • Proto-Oncogene Proteins
  • RNA, Messenger
  • Angiotensinogen
  • Angiotensin II
  • Vitamin D
  • 25-hydroxyvitamin D
  • Creatinine
  • Renin