Vitamin D depletion aggravates hypertension and target-organ damage.
Vitamin D depletion aggravates hypertension and target-organ damage.
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DOI：
10.1161/jaha.114.001417
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发表时间：
2015-01-28
影响因子：
5.4
通讯作者：
Dechend R
中科院分区：
文献类型：
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作者：
Andersen LB;Przybyl L;Haase N;von Versen-Höynck F;Qadri F;Jørgensen JS;Sorensen GL;Fruekilde P;Poglitsch M;Szijarto I;Gollasch M;Peters J;Muller DN;Christesen HT;Dechend R
我们测试了一个有争议的假设，即维生素 D 缺乏会通过影响肾素而加重高血压和靶器官损伤。由于人肾素 (hREN) 和血管紧张素原 (hAGT) 基因过度表达而产生过量血管紧张素 (Ang) II 的四周大双转基因大鼠 (dTGR) 接受维生素 D 耗尽 (n=18) 或标准饲料 (n=15) 3 周。耗尽组的血清 25-羟基维生素 D 水平非常低（平均值±SEM；3.8±0.29 与 40.6±1.19 nmol/L），并且在第 5 周时平均收缩压较高（158±3.5 与 134.6±3.7 mm Hg，P<0.001），第 6 周（176.6±3.3 与162.3±3.8 mm Hg，P<0.01）和第 7 周（171.6±5.1 与 155.9±4.3 mm Hg，P<0.05）。维生素 D 消耗导致相对心脏重量增加和血清肌酐浓度增加。此外，钠尿肽、中性粒细胞明胶酶相关脂质运载蛋白、hREN 和 rRen 的 mRNA 因维生素 D 消耗而增加。脾脏和循环系统中的调节性 T 细胞未受影响。维生素 D 缺乏组中的血管紧张素代谢产物，包括血管紧张素 II 和反调节分解产物血管紧张素 1 至 7，显着上调，而 ACE-1 和 ACE-2 活性不受影响。短期严重维生素 D 缺乏会加重 dTGR 中的高血压和靶器官损伤。我们的数据表明，即使是短期严重维生素 D 缺乏也可能直接促进高血压并影响肾素-血管紧张素系统成分，从而导致靶器官损伤。这些发现进一步证明维生素 D 缺乏也会影响人类高血压。
We tested the controversial hypothesis that vitamin D depletion aggravates hypertension and target‐organ damage by influencing renin. Four‐week‐old double‐transgenic rats (dTGR) with excess angiotensin (Ang) II production due to overexpression of the human renin (hREN) and angiotensinogen (hAGT) genes received vitamin D‐depleted (n=18) or standard chow (n=15) for 3 weeks. The depleted group had very low serum 25‐hydroxyvitamin D levels (mean±SEM; 3.8±0.29 versus 40.6±1.19 nmol/L) and had higher mean systolic BP at week 5 (158±3.5 versus 134.6±3.7 mm Hg, P<0.001), week 6 (176.6±3.3 versus 162.3±3.8 mm Hg, P<0.01), and week 7 (171.6±5.1 versus 155.9±4.3 mm Hg, P<0.05). Vitamin D depletion led to increased relative heart weights and increased serum creatinine concentrations. Furthermore, the mRNAs of natriuretic peptides, neutrophil gelatinase‐associated lipocalin, hREN, and rRen were increased by vitamin D depletion. Regulatory T cells in the spleen and in the circulation were not affected. Ang metabolites, including Ang II and the counter‐regulatory breakdown product Ang 1 to 7, were significantly up‐regulated in the vitamin D‐depleted groups, while ACE‐1 and ACE‐2 activities were not affected. Short‐term severe vitamin D depletion aggravated hypertension and target‐organ damage in dTGR. Our data suggest that even short‐term severe vitamin D deficiency may directly promote hypertension and impacts on renin‐angiotensin system components that could contribute to target‐organ damage. The findings add to the evidence that vitamin D deficiency could also affect human hypertension.