Vitamin D insufficiency is associated with impaired vascular endothelial and smooth muscle function and hypertension in young rats

J Physiol. 2011 Oct 1;589(Pt 19):4777-86. doi: 10.1113/jphysiol.2011.214726. Epub 2011 Aug 1.


Increasing evidence links vitamin D deficiency and cardiovascular dysfunction in human adults. There is a worldwide increase in the prevalence of vitamin D deficiency in women of reproductive age, particularly dark-skinned and/or veiled women and their infants. We used a rat model to determine the functional impact of vitamin D deficiency during intra uterine and early life on resistance artery reactivity and blood pressure in the offspring as young adults. Rat dams were maintained on vitamin D deficient or replete chow before and during pregnancy and lactation. The offspring were maintained on the same chow until studied at 7-8 weeks of age. Conscious blood pressure was measured. Endothelial and smooth muscle function were tested in mesenteric arteries on a pressure myograph. Vitamin D deficient male and female offspring had a 10-fold lower serum 25-hydroxyvitamin D (P < 0.0001) and markedly elevated blood pressures (11-20 mmHg, P < 0.001) and heart rates (21-40 beats min(-1), P < 0.02) than control fed offspring. Serum calcium was unchanged. Mesenteric artery myogenic tone was doubled in vitamin D deficiency. Endothelium-derived nitric oxide-evoked dilation was halved in arteries from vitamin D deficient males and dioestrous females. Dilation attributed to endothelium-derived hyperpolarizing factor was all but abolished in vitamin D deficient oestrous females. Nitroprusside-evoked dilation was unaltered in arteries from males, but was markedly reduced in vessels of vitamin D deplete females. In conclusion, early life vitamin D deficiency is associated with endothelial vasodilator dysfunction, and this is likely to contribute to the accompanying elevation in blood pressure and an increased cardiovascular disease risk.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Biological Factors / metabolism
  • Blood Pressure / drug effects
  • Blood Pressure / physiology
  • Body Weight / drug effects
  • Body Weight / physiology
  • Endothelium, Vascular / drug effects
  • Endothelium, Vascular / metabolism
  • Endothelium, Vascular / physiopathology*
  • Female
  • Heart Rate / drug effects
  • Heart Rate / physiology
  • Hypertension / metabolism
  • Hypertension / physiopathology*
  • Male
  • Mesenteric Arteries / drug effects
  • Mesenteric Arteries / metabolism
  • Mesenteric Arteries / physiopathology
  • Muscle Contraction / physiology
  • Muscle, Smooth, Vascular / drug effects
  • Muscle, Smooth, Vascular / metabolism
  • Muscle, Smooth, Vascular / physiopathology*
  • Nitric Oxide / metabolism
  • Nitroprusside / pharmacology
  • Prostaglandins / metabolism
  • Rats
  • Rats, Sprague-Dawley
  • Vasodilation / drug effects
  • Vasodilation / physiology
  • Vitamin D / analogs & derivatives
  • Vitamin D / blood
  • Vitamin D / metabolism
  • Vitamin D Deficiency / metabolism
  • Vitamin D Deficiency / physiopathology*


  • Biological Factors
  • Prostaglandins
  • endothelium-dependent hyperpolarization factor
  • Vitamin D
  • Nitroprusside
  • Nitric Oxide
  • 25-hydroxyvitamin D