Dietary salt regulates epithelial sodium channels in rat endothelial cells: adaptation of vasculature to salt

• Published in: British journal of pharmacology Vol. 172; no. 23; pp. 5634 - 5646
• Main Authors: 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
• Format: Journal Article
• Language: English
• Published: England Blackwell Publishing Ltd 01.12.2015; John Wiley and Sons Inc
• Subjects: Adaptation, Physiological - drug effects; Animals; Blood Pressure - drug effects; Endothelial Cells - drug effects; Endothelial Cells - metabolism; Epithelial Sodium Channels - metabolism; Hypertension - chemically induced; Hypertension - metabolism; Male; Rats; Rats, Sprague-Dawley; Research Paper; Rodents; Sodium; Sodium Chloride, Dietary - administration & dosage; Sodium Chloride, Dietary - pharmacology; Themed Section: Research Papers
• ISSN: 0007-1188; 1476-5381
• DOI: 10.1111/bph.13185

Background and Purpose 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. Experimental Approach 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. Key Results 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. Conclusions and Implications 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. Linked Articles This article is part of a themed section on Chinese Innovation in Cardiovascular Drug Discovery. To view the other articles in this section visit http://dx.doi.org/10.1111/bph.2015.172.issue-23