title: Vitamin d receptor activation mitigates the impact of uremia on endothelial function in the 5/6 nephrectomized rats.
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 (-50.0 +/- 7.4% in NX rats versus -96.2 +/- 5.3% in SHAM at 30 muM acetylcholine). The endothelial-dependent relaxation was improved to -58.2 +/- 6.0%, -77.5 +/- 7.3%, and -90.5 +/- 4.0% in NX rats treated with paricalcitol at 0.021, 0.042, and 0.083 mug/kg for two weeks, respectively, while paricalcitol at 0.042 mug/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.
authors.affiliation: Department of Pharmacy Practice, University of Illinois at Chicago, Chicago, IL 60612-7230, USA.
authors.forename: J Ruth
authors.initials: JR
authors.lastname: Wu-Wong
authors.forename: William
authors.initials: W
authors.lastname: Noonan
authors.forename: Masaki
authors.initials: M
authors.lastname: Nakane
authors.forename: Kristin A
authors.initials: KA
authors.lastname: Brooks
authors.forename: Jason A
authors.initials: JA
authors.lastname: Segreti
authors.forename: James S
authors.initials: JS
authors.lastname: Polakowski
authors.forename: Bryan
authors.initials: B
authors.lastname: Cox