Vitamin D (vitD) receptor (VDR) regulates the expression of several genes involved in signaling pathways affected in pulmonary hypertension (PH). VitD deficiency is highly prevalent in PH, and low levels are associated with poor prognosis. We investigated if vitD deficiency may predispose to or exacerbate PH. Male Wistar rats were fed with a standard or a vitD-free diet for five weeks. Then, rats were further divided into controls or PH, which was induced by a single dose of Su5416 (20 mg/kg) and exposure to hypoxia (10% O₂) for 2 weeks. VitD deficiency had no effect on pulmonary pressure in normoxic rats indicating that, by itself, it does not trigger PH. However, it induced several moderate but significant changes characteristic of PH in the pulmonary arteries, such as increased muscularization, endothelial dysfunction, increased survivin, reduced Bmp4, Bmp6, Ddit4 and Kcnk3 expression. Myocytes isolated from pulmonary arteries from vitD deficient rats had a reduced whole voltage-dependent potassium current density and acid-sensitive (TASK-like) potassium currents. In rats with PH induced by Su5416 plus hypoxia, vitD-free diet induced a modest increase in pulmonary pressure, worsened endothelial function, increased the hyperreactivity to serotonin, arterial muscularization, decreased total and TASK-1 potassium currents and further depolarized the pulmonary artery smooth muscle cell membrane. In human pulmonary artery smooth muscle cells from controls and patients with PH, the active form of vitD calcitriol significantly increased the KCNK3 mRNA expression. Altogether, these data strongly suggest that the deficit in vitD induces pulmonary vascular dysfunction.

中文翻译：

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维生素D缺乏会下调TASK-1通道并诱发肺血管功能障碍。

维生素D（vitD）受体（VDR）调节参与肺动脉高压（PH）的信号通路的几种基因的表达。VitD缺乏症在PH中非常普遍，低水平与预后不良相关。我们调查了vitD缺乏是否可能诱发或加剧PH。给雄性Wistar大鼠喂食标准饮食或不含vitD的食物五周。然后，将大鼠进一步分为对照组或PH，由单一剂量的Su5416（20 mg / kg）和暴露于缺氧（10％O ₂）诱导） 2个礼拜。VitD缺乏症对常氧大鼠的肺压没有影响，表明它本身不会触发PH。然而，它诱导了肺动脉PH的一些中度但显着的变化，例如肌肉增加，内皮功能障碍，survivin增加，Bmp4，Bmp6，Ddit4和Kcnk3表达降低。从vitD缺陷大鼠的肺动脉中分离出的心肌细胞，其全电压依赖性钾电流密度和酸敏感性（TASK样）钾电流均降低。在Su5416加上缺氧诱导的PH大鼠中，无vitD饮食会引起肺动脉压力适度升高，内皮功能恶化，对血清素的过度反应性，动脉肌肉化，总钾电流和TASK-1钾电流降低，并进一步使肺动脉平滑肌细胞膜去极化。在来自对照组和PH患者的人肺动脉平滑肌细胞中，vitD骨化三醇的活性形式显着增加了KCNK3 mRNA的表达。总之，这些数据强烈表明，vitD的缺乏会诱发肺血管功能障碍。