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International Journal of Endocrinology
Volume 2010 (2010), Article ID 625852, 10 pages
http://dx.doi.org/10.1155/2010/625852
Research Article

Vitamin D Receptor Activation Mitigates the Impact of Uremia on Endothelial Function in the 5/6 Nephrectomized Rats

1Department of Pharmacy Practice, University of Illinois at Chicago, Chicago, IL 60612-7230, USA
2Abbott Laboratories, Renal Care, Abbott Park, IL 60048, USA
3VidaGene, VDR Project, Chicago, IL 60612, USA

Received 29 March 2009; Revised 29 September 2009; Accepted 28 October 2009

Academic Editor: Yan Chun Li

Copyright © 2010 J. Ruth Wu-Wong et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Endothelial dysfunction increases cardiovascular disease risk in chronic kidney disease (CKD). This study investigates whether VDR activation affects endothelial function in CKD. The 5/6 nephrectomized (NX) rats with experimental chronic renal insufficiency were treated with or without paricalcitol, a VDR activator. Thoracic aortic rings were precontracted with phenylephrine and then treated with acetylcholine or sodium nitroprusside. Uremia significantly affected aortic relaxation ( 5 0 . 0 ± 7 . 4 % in NX rats versus 9 6 . 2 ± 5 . 3 % in SHAM at 30  𝜇 M acetylcholine). The endothelial-dependent relaxation was improved to – 5 8 . 2 ± 6 . 0 %, – 7 7 . 5 ± 7 . 3 %, and – 9 0 . 5 ± 4 . 0 % in NX rats treated with paricalcitol at 0.021, 0.042, and 0.083  𝜇 g/kg for two weeks, respectively, while paricalcitol at 0.042  𝜇 g/kg did not affect blood pressure and heart rate. Parathyroid hormone (PTH) suppression alone did not improve endothelial function since cinacalcet suppressed PTH without affecting endothelial-dependent vasorelaxation. N-omega-nitro-L-arginine methyl ester completely abolished the effect of paricalcitol on improving endothelial function. These results demonstrate that VDR activation improves endothelial function in CKD.