Activated vitamin D attenuates left ventricular abnormalities induced by dietary sodium in Dahl salt-sensitive animals
Activated vitamin D attenuates left ventricular abnormalities induced by dietary sodium in Dahl salt-sensitive animals
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DOI：
10.1073/pnas.0611202104
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发表时间：
2007-10-23
影响因子：
11.1
通讯作者：
Kang, Peter M.
中科院分区：
文献类型：
--
作者：
Bodyak, Natalya;Ayus, Juan Carlos;Kang, Peter M.
在血液透析患者中的观察结果表明，活化维生素D治疗具有生存优势。左心室（LV）结构和功能异常与血液透析死亡率密切相关。在本研究中，我们研究了帕立骨化醇（PC，119-nor-1，25（OH）（2）D-2）（一种活化维生素D化合物）是否能减弱Dahl盐敏感（DSS）大鼠LV异常的发生，以及人类是否表现出相似的结果。与喂食高盐（HS）饮食（6周6%NaCl）的DSS大鼠相比，HS+PC与较低的心脏和肺重量，降低LV质量，后壁厚度和舒张末期压力，以及缩短分数增加相关。HS组之间的血压没有显著差异。HS+PC动物的血浆脑钠肽水平和心脏脑钠肽、心钠素和肾素的mRNA表达显著降低。基因芯片分析显示45个特异性HS基因被PC修饰。在一项血液透析患者的回顾性初步研究中，与未经治疗的患者相比，经超声心动图检查，PC治疗的受试者显示舒张功能改善，LV间隔和后壁厚度降低。总之，PC减弱DSS大鼠LV改变的发展，这些作用应在人体临床试验中进行检查。
Observations in hemodialysis patients suggest a survival advantage associated with activated vitamin D therapy. Left ventricular (LV) structural and functional abnormalities are strongly linked with hemodialysis mortality. Here, we investigated whether paricalcitol (PC, 119-nor-1,25(OH)(2)D-2), an activated vitamin D compound, attenuates the development of LV abnormalities in the Dahl salt-sensitive (DSS) rat and whether humans demonstrate comparable findings. Compared with DSS rats fed a high-salt (HS) diet(6% NaCl for 6 weeks), HS+PC was associated with lower heart and lung weights, reduced LV mass, posterior wall thickness and end diastolic pressures, and increased fractional shortening. Blood pressures did not significantly differ between the HS groups. Plasma brain natriuretic peptide levels, and cardiac mRNA expression of brain natriuretic peptide, atrial natriuretic factor, and renin were significantly reduced in the HS+PC animals. Microarray analyses revealed 45 specific HS genes modified by PC. In a retrospective pilot study of hemodialysis patients, PC-treated subjects demonstrated improved diastolic function and a reduction in LV septal and posterior wall thickness by echocardiography compared with untreated patients. In summary, PC attenuates the development of LV alterations in DSS rats, and these effects should be examined in human clinical trials.