A calcimimetic (R-568), but not calcitriol, prevents vascular remodeling in uremia.
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.
Koleganova
Nadezda
N
Department of Internal Medicine, University of Heidelberg, Heidelberg, Germany. nad_ko@gmx.de
Piecha
Grzegorz
G
Ritz
Eberhard
E
Schmitt
Claus Peter
CP
Gross
Marie-Luise
ML
D000814:Aniline Compounds / Q000494:pharmacology* / Q000627:therapeutic use; D000818:Animals; D001011:Aorta / Q000473:pathology; D002114:Calcinosis; D002117:Calcitriol / Q000494:pharmacology* / Q000627:therapeutic use; D002118:Calcium / Q000819:agonists; D049109:Cell Proliferation; D004730:Endothelium, Vascular / Q000473:pathology; D005786:Gene Expression Regulation / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000473:pathology; D010627:Phenethylamines; D011437:Propylamines; D051381:Rats; D017207:Rats, Sprague-Dawley; D018167:Receptors, Calcitriol / Q000235:genetics; D044169:Receptors, Calcium-Sensing / Q000235:genetics; D051437:Renal Insufficiency / Q000150:complications / Q000473:pathology; D014511:Uremia / Q000188:drug therapy* / Q000473:pathology
D000814:Aniline Compounds; C107873:N-(2-chlorophenylpropyl)-1-(3-methoxyphenyl)ethylamine; D010627:Phenethylamines; D011437:Propylamines; D018167:Receptors, Calcitriol; D044169:Receptors, Calcium-Sensing; D002117:Calcitriol; D002118:Calcium