title: Dietary salt regulates epithelial sodium channels in rat endothelial cells: adaptation of vasculature to salt.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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.
  
  
  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
  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.
authors.affiliation: 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.
authors.forename: Hui-Bin
authors.initials: HB
authors.lastname: Liu
authors.affiliation: 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.
authors.forename: Jun
authors.initials: J
authors.lastname: Zhang
authors.affiliation: 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.
authors.forename: Ying-Ying
authors.initials: YY
authors.lastname: Sun
authors.affiliation: 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.
authors.forename: Xin-Yuan
authors.initials: XY
authors.lastname: Li
authors.affiliation: 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.
authors.forename: Shuai
authors.initials: S
authors.lastname: Jiang
authors.affiliation: Department of Pharmacology, Harbin Medical University, Harbin, China.
authors.forename: Ming-Yu
authors.initials: MY
authors.lastname: Liu
authors.affiliation: 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.
authors.forename: Jing
authors.initials: J
authors.lastname: Shi
authors.affiliation: 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.
authors.forename: Bin-Lin
authors.initials: BL
authors.lastname: Song
authors.affiliation: 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.
authors.forename: Dan
authors.initials: D
authors.lastname: Zhao
authors.affiliation: Department of Physiology, Emory University School of Medicine, Atlanta, GA, USA.
authors.forename: He-Ping
authors.initials: HP
authors.lastname: Ma
authors.affiliation: 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.
authors.forename: Zhi-Ren
authors.initials: ZR
authors.lastname: Zhang
mesh_terms: D000222:Adaptation, Physiological / Q000187:drug effects*; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D042783:Endothelial Cells / Q000187:drug effects* / Q000378:metabolism*; D053503:Epithelial Sodium Channels / Q000378:metabolism*; D006973:Hypertension / Q000139:chemically induced / Q000378:metabolism; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D017673:Sodium Chloride, Dietary / Q000008:administration & dosage / Q000494:pharmacology*
chemical_list: D053503:Epithelial Sodium Channels; D017673:Sodium Chloride, Dietary