Funato Yosuke, Yamazaki Daisuke, Miki Hiroaki
Department of Cellular Regulation, Research Institute for Microbial Diseases, Osaka University, Suita, Osaka, Japan.
J Hypertens. 2017 Mar;35(3):585-592. doi: 10.1097/HJH.0000000000001211.
Epidemiological studies have shown that magnesium intake/excretion is inversely correlated with blood pressure (BP), and artificial supplementation of magnesium was able to prevent hypertension. However, there has been no molecular genetic study showing the importance of magnesium homeostasis in BP regulation.
We analyzed magnesium content and BP of mice lacking genes encoding cyclin M (CNNM) Mg transporter family proteins.
Systemic heterozygotes and the kidney-specific homozygotes for Cnnm2-deficient alleles are both viable and show hypomagnesemia, indicating the important function of CNNM2 in maintaining magnesium homeostasis in the kidney. Endogenous CNNM2 localizes at the basolateral membrane of kidney distal convoluted tubule cells, which play important roles not only in magnesium reabsorption but also in BP control. The BP of these viable strains is significantly reduced; the SBP values by telemetric measurements are 121.7 ± 2.8 mmHg in wild-type, and 110.2 ± 2.7 and 109.7 ± 3.6 mmHg in systemic heterozygotes and kidney-specific homozygotes, respectively.
Analyses of mice lacking CNNM Mg transporters clearly demonstrated abnormalities in BP values, confirming the importance of magnesium homeostasis in maintaining BP.
流行病学研究表明，镁的摄入/排泄与血压（BP）呈负相关，人工补充镁能够预防高血压。然而，尚无分子遗传学研究表明镁稳态在血压调节中的重要性。
我们分析了缺乏编码细胞周期蛋白M（CNNM）镁转运蛋白家族蛋白基因的小鼠的镁含量和血压。
Cnnm2缺陷等位基因的全身杂合子和肾脏特异性纯合子均存活，并表现出低镁血症，表明CNNM2在维持肾脏镁稳态中具有重要作用。内源性CNNM2定位于肾脏远曲小管细胞的基底外侧膜，该细胞不仅在镁重吸收中起重要作用，而且在血压控制中也起重要作用。这些存活品系的血压显著降低；通过遥测测量的收缩压值在野生型中为121.7±2.8 mmHg，在全身杂合子和肾脏特异性纯合子中分别为110.2±2.7和109.7±3.6 mmHg。
对缺乏CNNM镁转运蛋白的小鼠的分析清楚地表明了血压值异常，证实了镁稳态在维持血压中的重要性。
