Liu Hui-Bin, Zhang Jun, Sun Ying-Ying, Li Xin-Yuan, Jiang Shuai, Liu Ming-Yu, Shi Jing, Song Bin-Lin, Zhao Dan, Ma He-Ping, Zhang Zhi-Ren
Departments of Clinical Pharmacy and Cardiology, Institute of Clinical Pharmacy, the 2nd Affiliated Hospital, Harbin Medical University, Key Laboratories of Education Ministry for Myocardial Ischemia Mechanism and Treatment, Harbin, China.
Department of Pharmacology, Harbin Medical University, Harbin, China.
Br J Pharmacol. 2015 Dec;172(23):5634-46. doi: 10.1111/bph.13185. Epub 2015 Jun 26.
The epithelial sodium channel (ENaC) is expressed in vascular endothelial cells and is a negative modulator of vasodilation. However, the role of endothelial ENaCs in salt-sensitive hypertension remains unclear. Here, we have investigated how endothelial ENaCs in Sprague-Dawley (SD) rats respond to high-salt (HS) challenge.
BP and plasma aldosterone levels were measured. We used patch-clamp technique to record ENaC activity in split-open mesenteric arteries (MAs). Western blot and Griess assay were used to detect expression of α-ENaCs, eNOS and NO. Vasorelaxation in second-order MAs was measured with wire myograph assays.
Functional ENaCs were observed in endothelial cells and their activity was significantly decreased after 1 week of HS diet. After 3 weeks of HS diet, ENaC expression was also reduced. When either ENaC activity or expression was reduced, endothelium-dependent relaxation (EDR) of MAs, in response to ACh, was enhanced. This enhancement of EDR was mimicked by amiloride, a blocker of ENaCs. By contrast, HS diet significantly increased contractility of MAs, accompanied by decreased eNOS activity and NO levels. However, ACh-induced release of NO was much higher in MAs isolated from HS rats than those from NS rats.
HS intake increased the BP of SD rats, but simultaneously enhanced EDR by reducing ENaC activity and expression due to feedback inhibition. Therefore, ENaCs may play an important role in endothelial cells allowing the vasculature to adapt to HS conditions.
上皮钠通道（ENaC）在血管内皮细胞中表达，是血管舒张的负性调节因子。然而，内皮ENaC在盐敏感性高血压中的作用仍不清楚。在此，我们研究了Sprague-Dawley（SD）大鼠的内皮ENaC如何应对高盐（HS）刺激。
测量血压和血浆醛固酮水平。我们使用膜片钳技术记录分离的肠系膜动脉（MA）中的ENaC活性。采用蛋白质免疫印迹法和格里斯试剂法检测α-ENaC、内皮型一氧化氮合酶（eNOS）和一氧化氮（NO）的表达。用线肌动描记法检测二级MA中的血管舒张情况。
在内皮细胞中观察到功能性ENaC，高盐饮食1周后其活性显著降低。高盐饮食3周后，ENaC表达也降低。当ENaC活性或表达降低时，MA对乙酰胆碱（ACh）的内皮依赖性舒张（EDR）增强。ENaC阻滞剂氨氯吡咪可模拟这种EDR增强。相比之下，高盐饮食显著增加了MA的收缩性，同时伴有eNOS活性和NO水平降低。然而，从高盐大鼠分离的MA中，ACh诱导的NO释放比从正常盐大鼠分离的MA中高得多。
摄入高盐可升高SD大鼠的血压，但同时通过反馈抑制降低ENaC活性和表达来增强EDR。因此，ENaC可能在内皮细胞中发挥重要作用，使血管系统能够适应高盐环境。
