Cardiovascular Division, Beth Israel Deaconess Med Center, Boston, MA 02215, USA.
J Card Fail. 2011 Dec;17(12):1051-8. doi: 10.1016/j.cardfail.2011.08.006. Epub 2011 Sep 9.
Activated vitamin D analog, paricalcitol, has been shown to attenuate the development of cardiac hypertrophy in Dahl salt sensitive (DSS) rats. To determine whether an antihypertrophic effect is class specific, we tested if doxercalciferol (a pro-hormone vitamin D2 analog) could also attenuate the development of cardiac hypertrophy in DSS rats.
Male DSS rats were fed a high salt (HS) diet for 6 weeks beginning at 6 weeks of age. Doxercalciferol was administered intraperitoneally at 150 ng, 3 times per week (Monday, Wednesday, Friday) for 6 weeks. Pathological and echocardiographic findings demonstrated that rats on HS diet with doxercalciferol administration had significant decrease in cardiac hypertrophy and improved cardiac function compared to the HS + vehicle. In addition, there was a significant decrease in plasma brain natriuretic peptide (BNP) level and tissue atrial natriuretic factor (ANF) mRNA level with doxercalciferol treatment. Doxercalciferol also significantly reduced the level of protein kinase C-α (PKCα) suggesting that PKC-mediated cardiac hypertrophy may be associated with vitamin D deficiency.
Administration of doxercalciferol attenuated the development of HS diet induced cardiac hypertrophy and cardiac dysfunction in DSS rats.
已证实活化维生素 D 类似物帕立骨化醇可减轻 Dahl 盐敏感（DSS）大鼠心脏肥大的发展。为确定抗肥厚作用是否具有类特异性，我们检测了 doxercalciferol（一种前激素维生素 D2 类似物）是否也可减轻 DSS 大鼠心脏肥大的发展。
雄性 DSS 大鼠在 6 周龄时开始给予高盐（HS）饮食 6 周。 doxercalciferol 每周 3 次（周一、周三、周五）经腹腔内给予 150ng，共 6 周。病理和超声心动图结果表明，与 HS+载体组相比，给予 doxercalciferol 的 HS 饮食大鼠的心脏肥大显著减少，心功能得到改善。此外， doxercalciferol 治疗还显著降低了血浆脑钠肽（BNP）水平和组织心房利钠肽（ANF）mRNA 水平。 doxercalciferol 还显著降低了蛋白激酶 C-α（PKCα）的水平，提示 PKC 介导的心脏肥大可能与维生素 D 缺乏有关。
doxercalciferol 的给予可减轻 DSS 大鼠 HS 饮食诱导的心脏肥大和心功能障碍的发展。
