Department of Pharmacy Practice, University of Illinois at Chicago, Chicago, IL 60612-7230, USA.
Int J Endocrinol. 2010;2010:625852. doi: 10.1155/2010/625852. Epub 2010 Feb 10.
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.
内皮功能障碍增加慢性肾脏病 (CKD) 的心血管疾病风险。本研究探讨了维生素 D 受体 (VDR) 激活是否会影响 CKD 中的内皮功能。用 VDR 激活剂帕立骨化醇对 5/6 肾切除 (NX) 大鼠进行治疗，以模拟实验性慢性肾功能不全。用苯肾上腺素预收缩胸主动脉环，然后用乙酰胆碱或硝普钠处理。尿毒症显著影响主动脉松弛 (-50.0 +/- 7.4%在 NX 大鼠与 -96.2 +/- 5.3%在 SHAM 在 30 μM 乙酰胆碱)。内皮依赖性松弛在 NX 大鼠中分别改善至 -58.2 +/- 6.0%、-77.5 +/- 7.3%和-90.5 +/- 4.0%，在两周内用帕立骨化醇 0.021、0.042 和 0.083 μg/kg 治疗，而帕立骨化醇 0.042 μg/kg 对血压和心率没有影响。甲状旁腺激素 (PTH) 抑制本身并不能改善内皮功能，因为西那卡塞抑制 PTH 而不影响内皮依赖性血管舒张。N-ω-硝基-L-精氨酸甲酯完全消除了帕立骨化醇改善内皮功能的作用。这些结果表明 VDR 激活可改善 CKD 中的内皮功能。
