Guo Lirong, Meng Jie, Xuan Chengluan, Ge Jingyan, Sun Wenzhu, O'Rourke Stephen T, Sun Chengwen
Department of Pathophysiology, College of Basic Medical Sciences, and Second Hospital of Jilin University, Jilin University, Changchun, Jilin 130021, China; Department of Pharmaceutical Sciences, North Dakota State University, Fargo, ND 58105, USA.
Department of Pathophysiology, College of Basic Medical Sciences, and Second Hospital of Jilin University, Jilin University, Changchun, Jilin 130021, China.
Biochem Biophys Res Commun. 2015 May 29;461(2):254-9. doi: 10.1016/j.bbrc.2015.04.010. Epub 2015 Apr 11.
Elevated Na(+) concentration ([Na(+)]) in the cerebrospinal fluid (CSF) contributes to the development of salt-sensitive hypertension. CSF is formed by the choroid plexus (CP) in cerebral ventricles, and [Na(+)] in CSF is controlled by transporters in CP. Here, we examined the effect of high salt diet on the expression of urea transporters (UTs) in the CP of Dahl S vs Dahl R rats using real time PCR. High salt intake (8%, for 2 weeks) did not alter the mRNA levels of UT-A (encoded by SLC14A2 gene) in the CP of either Dahl S or Dahl R rats. In contrast, the mRNA levels of UT-B (encoded by SLC14A1 gene) were significantly reduced in the CP of Dahl S rats on high salt diet as compared with Dahl R rats or Dahl S rats on normal salt diet. Reduced UT-B expression was associated with increased [Na(+)] in the CSF and elevated mean arterial pressure (MAP) in Dahl S rats treated with high salt diet, as measured by radiotelemetry. High salt diet-induced reduction in UT-B protein expression in the CP of Dahl S rats was confirmed by Western blot. Immunohistochemistry using UT-B specific antibodies demonstrated that UT-B protein was expressed on the epithelial cells in the CP. These data indicate that high salt diet induces elevations in CSF [Na(+)] and in MAP, both of which are associated with reduced UT-B expression in the CP of Dahl S rats, as compared with Dahl R rats. The results suggest that altered UT-B expression in the CP may contribute to an imbalance of water and electrolytes in the CSF of Dahl S rats on high salt diet, thereby leading to alterations in MAP.
脑脊液(CSF)中升高的钠离子浓度([Na⁺])会促使盐敏感性高血压的发展。脑脊液由脑室中的脉络丛(CP)形成,脑脊液中的[Na⁺]由脉络丛中的转运蛋白控制。在此,我们使用实时PCR检测了高盐饮食对Dahl S大鼠与Dahl R大鼠脉络丛中尿素转运体(UTs)表达的影响。高盐摄入(8%,持续两周)并未改变Dahl S大鼠或Dahl R大鼠脉络丛中UT-A(由SLC14A2基因编码)的mRNA水平。相比之下,与Dahl R大鼠或正常盐饮食的Dahl S大鼠相比,高盐饮食的Dahl S大鼠脉络丛中UT-B(由SLC14A1基因编码)mRNA水平显著降低。通过无线电遥测法测量发现,高盐饮食的Dahl S大鼠中UT-B表达降低与脑脊液中[Na⁺]升高及平均动脉压(MAP)升高有关。蛋白质免疫印迹法证实了高盐饮食导致Dahl S大鼠脉络丛中UT-B蛋白表达降低。使用UT-B特异性抗体的免疫组织化学表明,UT-B蛋白在脉络丛上皮细胞上表达。这些数据表明,与Dahl R大鼠相比,高盐饮食会导致Dahl S大鼠脑脊液中[Na⁺]和MAP升高,二者均与脉络丛中UT-B表达降低有关。结果表明,脉络丛中UT-B表达改变可能导致高盐饮食的Dahl S大鼠脑脊液中水和电解质失衡,从而导致MAP改变。