Barbuskaite Dagne, Pedersen Fredrik D, Christensen Henriette L, Johnsen Laura Ø, Praetorius Jeppe, Damkier Helle H
Department of Cellular and Molecular Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
Department of Biomedicine, Health, Aarhus University, Aarhus, Denmark.
Front Physiol. 2020 May 29;11:560. doi: 10.3389/fphys.2020.00560. eCollection 2020.
Arterial hypertension, is a common disorder with multiple and variable etiologies. Single nucleotide polymorphism analyses have detected an association between variants in the gene encoding the electrogenic Na:HCO cotransporter NBCe2 (), and salt-sensitive hypertension. Mice with genetic deletion of NBCe2 are hypertensive, and the cause of the blood pressure (BP) increase is believed to arise from a lack of renal NBCe2 function. The exact cellular expression of NBCe2 in the kidney tubular system is, however, not determined. Here, we find NBCe2 to be expressed predominantly in isolated connecting tubules (CNT) and cortical collecting ducts (CD) by RT-PCR. In isolated renal CNT and CCD, genetic deletion of NBCe2 leads to decreased net base extrusion. To determine the role of renal NBCe2 in the development of hypertension, we generated CNT and intercalated cell NBCe2 knockout mice by crossing an lox mouse with mice expressing cre recombinase under the V-ATPase B1 subunit promotor. Although the mice displayed changes in the expression of renal membrane transporters, we did not detect hypertension in these mice by tail cuff recordings. In conclusion, while global NBCe2 deletion certainly causes hypertension this study cannot confirm the role of renal NBCe2 expression in blood pressure regulation.
动脉高血压是一种病因多样的常见病症。单核苷酸多态性分析已检测到编码电中性钠-碳酸氢根共转运体NBCe2（）的基因变异与盐敏感性高血压之间存在关联。基因敲除NBCe2的小鼠患有高血压，血压升高的原因被认为是由于肾脏中缺乏NBCe2功能。然而，NBCe2在肾小管系统中的具体细胞表达尚未确定。在此，我们通过逆转录聚合酶链反应发现NBCe2主要在分离的连接小管（CNT）和皮质集合管（CD）中表达。在分离的肾CNT和CCD中，基因敲除NBCe2导致净碱排出减少。为了确定肾脏NBCe2在高血压发生中的作用，我们通过将lox小鼠与在V-ATPase B1亚基启动子控制下表达cre重组酶的小鼠杂交，培育出了CNT和闰细胞NBCe2基因敲除小鼠。尽管这些小鼠的肾膜转运体表达出现了变化，但通过尾套法记录，我们并未在这些小鼠中检测到高血压。总之，虽然全身性敲除NBCe2肯定会导致高血压，但本研究无法证实肾脏中NBCe2的表达在血压调节中的作用。
