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 (% in NX rats versus % in SHAM at 30 M acetylcholine). The endothelial-dependent relaxation was improved to –%, –%, and –% in NX rats treated with paricalcitol at 0.021, 0.042, and 0.083 g/kg for two weeks, respectively, while paricalcitol at 0.042 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.
Cardiovascular disease risk and comparison of different strategies for blood pressure management in rural India
