A calcimimetic (R-568), but not calcitriol, prevents vascular remodeling in uremia

Kidney Int. 2009 Jan;75(1):60-71. doi: 10.1038/ki.2008.490. Epub 2008 Oct 1.


Renal insufficiency increases cardiovascular risk, accelerates atherogenesis, and causes vascular wall remodeling. Here we evaluated the effect of the calcimimetic R-568 and non-hypercalcemic doses of calcitriol on vascular structure. Subtotal nephrectomy was produced in Sprague-Dawley rats followed by treatment with R-568, calcitriol, or vehicle for 12 weeks. The aortic wall was significantly thicker in vehicle-treated uremic rats than in those with a sham-operation but R-568-treated uremic rats had a lower value. In contrast, calcitriol increased wall thickness in both the sham-operated and uremic groups. The calcification score, measured by von Kossa staining, and the number of proliferating cells in the intima and media were significantly higher in the calcitriol-treated uremic group. The expression of the calcium sensing receptor was higher in the intima of sham-operated and uremic rats treated with R-568 compared to animals treated with vehicle or calcitriol, while the expression of the vitamin D receptor was upregulated by both calcitriol and R-568. Our study shows that in uremic rats, calcitriol increased while R-568 attenuated media calcification and proliferation of vascular smooth muscle and endothelial cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aniline Compounds / pharmacology*
  • Aniline Compounds / therapeutic use
  • Animals
  • Aorta / pathology
  • Calcinosis
  • Calcitriol / pharmacology*
  • Calcitriol / therapeutic use
  • Calcium / agonists
  • Cell Proliferation
  • Endothelium, Vascular / pathology
  • Gene Expression Regulation / drug effects
  • Muscle, Smooth, Vascular / pathology
  • Phenethylamines
  • Propylamines
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, Calcitriol / genetics
  • Receptors, Calcium-Sensing / genetics
  • Renal Insufficiency / complications
  • Renal Insufficiency / pathology
  • Uremia / drug therapy*
  • Uremia / pathology


  • Aniline Compounds
  • N-(2-chlorophenylpropyl)-1-(3-methoxyphenyl)ethylamine
  • Phenethylamines
  • Propylamines
  • Receptors, Calcitriol
  • Receptors, Calcium-Sensing
  • Calcitriol
  • Calcium