Andersen Louise Bjørkholt, Przybyl Lukasz, Haase Nadine, von Versen-Höynck Frauke, Qadri Fatimunnisa, Jørgensen Jan Stener, Sorensen Grith Lykke, Fruekilde Palle, Poglitsch Marko, Szijarto István, Gollasch Maik, Peters Joerg, Muller Dominik N, Christesen Henrik Thybo, Dechend Ralf
Hans Christian Andersen Children's Hospital, Odense University Hospital, Denmark (L.B.A., H.T.C.) Institute of Clinical Research, University of Southern Denmark, Odense, Denmark (L.B.A., J.S., H.T.C.).
Experimental and Clinical Research Center, a joint cooperation between the Max-Delbruck Center for Molecular Medicine and the Charité Medical Faculty, Berlin, Germany (L.P., N.H., F.Q., I.S., M.G., D.N.M., R.D.).
J Am Heart Assoc. 2015 Jan 28;4(2):e001417. doi: 10.1161/JAHA.114.001417.
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.
我们检验了一个存在争议的假说，即维生素D缺乏通过影响肾素加重高血压和靶器官损害。
四周龄的双转基因大鼠（dTGR）由于人肾素（hREN）和血管紧张素原（hAGT）基因过表达而产生过量血管紧张素（Ang）II，将其分为两组，一组给予维生素D缺乏饮食（n = 18），另一组给予标准饮食（n = 15），持续3周。缺乏组血清25-羟基维生素D水平极低（均值±标准误；3.8±0.29对40.6±1.19 nmol/L），在第5周（158±3.5对134.6±3.7 mmHg，P<0.001）、第6周（176.6±3.3对162.3±3.8 mmHg，P<0.01）和第7周（171.6±5.1对155.9±4.3 mmHg，P<0.05）时平均收缩压更高。维生素D缺乏导致相对心脏重量增加和血清肌酐浓度升高。此外，维生素D缺乏使利钠肽、中性粒细胞明胶酶相关脂质运载蛋白、hREN和rRen的mRNA增加。脾脏和循环中的调节性T细胞未受影响。维生素D缺乏组中包括Ang II和反向调节分解产物Ang 1至7在内的Ang代谢产物显著上调，而ACE-1和ACE-2活性未受影响。
短期严重维生素D缺乏加重了dTGR的高血压和靶器官损害。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，进而导致靶器官损害。这些发现进一步证明维生素D缺乏也可能影响人类高血压。
