Vitamin D Receptor Activation Mitigates the Impact of Uremia on Endothelial Function in the 56 Nephrectomized Rats

Abstract EN

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 μM 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 μg/kg for two weeks, respectively, while paricalcitol at 0.042 μg/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.