Hui-Bin Liu1, Jun Zhang1, Ying-Ying Sun1, Xin-Yuan Li1, Shuai Jiang1, Ming-Yu Liu2, Jing Shi1, Bin-Lin Song1, Dan Zhao1, He-Ping Ma3, Zhi-Ren Zhang1. 1. 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. 2. Department of Pharmacology, Harbin Medical University, Harbin, China. 3. Department of Physiology, Emory University School of Medicine, Atlanta, GA, USA.
Abstract
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.
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 HSrats 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.
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