Vitamin D derivatives acutely reduce endothelium-dependent contractions in the aorta of the spontaneously hypertensive rat

Am J Physiol Heart Circ Physiol. 2008 Jul;295(1):H289-96. doi: 10.1152/ajpheart.00116.2008. Epub 2008 May 16.


The available evidence suggests that vitamin D has cardiovascular effects besides regulating calcium homeostasis. To examine the effect of 1,25-dihydroxyvitamin D(3), the major metabolite of vitamin D, on endothelium-dependent contractions, aortic rings of spontaneously hypertensive rats (SHR) were suspended in organ chambers for isometric force measurements. Rings were incubated with N(omega)-nitro-l-arginine methyl ester (l-NAME) and then exposed to increasing concentrations of acetylcholine, ATP, or the calcium ionophore to trigger contractions. This was done in the absence or presence of 1,25-dihydroxyvitamin D(3). The release of prostacyclin after acetylcholine or A-23187 stimulation was also measured. The cytosolic-free calcium concentration was measured by confocal microscopy after incubation with the fluorescent dyes fluo-4 and fura red. The presence of vitamin D receptors was confirmed using immunohistochemistry. Acetylcholine- and ATP-induced endothelium-dependent contractions were significantly reduced compared with those obtained in the absence of the drug. This effect was not present if A-23187 was used as an agonist. The acetylcholine- but not the A-23187-induced release of prostacyclin was reduced by the acute administration of 1,25-dihydroxyvitamin D(3). Exposure to 1,25-dihydroxyvitamin D(3) reduced the increase in cytosolic-free calcium concentration caused by acetylcholine but not by A-23187 in cells. Vitamin D receptors were densely distributed in the endothelium. Inecalcitol (19-nor-14-epi-23-yne-1,25-dihydroxyvitamin D(3)), a synthetic analog of vitamin D, caused a comparable depression of endothelium-dependent contractions as 1,25-dihydroxyvitamin D(3). These results demonstrate that vitamin D(3) modulates vascular tone by reducing calcium influx into the endothelial cells and hence decreasing the production of endothelium-derived contracting factors.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylcholine / pharmacology
  • Adenosine Triphosphate / metabolism
  • Animals
  • Calcimycin / pharmacology
  • Calcitriol / analogs & derivatives
  • Calcitriol / metabolism*
  • Calcium / metabolism
  • Disease Models, Animal
  • Dose-Response Relationship, Drug
  • Endothelium, Vascular / drug effects
  • Endothelium, Vascular / metabolism*
  • Endothelium, Vascular / physiopathology
  • Epoprostenol / metabolism
  • Hypertension / metabolism*
  • Hypertension / physiopathology
  • Immunohistochemistry
  • Microscopy, Confocal
  • Rats
  • Rats, Inbred SHR
  • Rats, Inbred WKY
  • Receptors, Calcitriol / agonists
  • Receptors, Calcitriol / metabolism
  • Vasoconstriction* / drug effects
  • Vasoconstrictor Agents / pharmacology
  • Vitamin D / analogs & derivatives
  • Vitamin D / metabolism*


  • Receptors, Calcitriol
  • Vasoconstrictor Agents
  • Vitamin D
  • Calcimycin
  • Adenosine Triphosphate
  • Epoprostenol
  • Calcitriol
  • Acetylcholine
  • Calcium