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

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

Author information

1
Department of Internal Medicine, University of Heidelberg, Heidelberg, Germany. nad_ko@gmx.de

Abstract

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.

PMID:
19092814
DOI:
10.1038/ki.2008.490
[Indexed for MEDLINE]
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