Dietary salt blunts vasodilation by stimulating epithelial sodium channels in endothelial cells from salt‐sensitive Dahl rats

Background and Purpose Our recent studies show that the reduced activity of epithelial sodium channels (ENaC) in endothelial cells accounts for the adaptation of vasculature to salt in Sprague–Dawley rats. The present study examines a hypothesis that enhanced ENaC activity mediates the loss of vasor...

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Published in:British journal of pharmacology 2018-04, Vol.175 (8), p.1305-1317
Main Authors: Wang, Zi‐Rui, Liu, Hui‐Bin, Sun, Ying‐Ying, Hu, Qing‐Qing, Li, Yu‐Xia, Zheng, Wei‐Wan, Yu, Chang‐Jiang, Li, Xin‐Yuan, Wu, Ming‐Ming, Song, Bin‐Lin, Mu, Jian‐Jun, Yuan, Zu‐Yi, Zhang, Zhi‐Ren, Ma, He‐Ping
Format: Article
Language:English
Subjects:
Aldosterone
Amiloride
Animals
Arteries
Blood pressure
Blood Pressure - drug effects
Cardiovascular diseases
Cells, Cultured
Diet
Endothelial cells
Endothelial Cells - drug effects
Endothelial Cells - physiology
Endothelium
Epithelial Sodium Channel Agonists - pharmacology
Epithelial Sodium Channels - physiology
Hypertension
Immunofluorescence
Male
Mesenteric Arteries - cytology
Nitric Oxide - metabolism
Nitric Oxide Synthase Type III - metabolism
Rats
Rats, Inbred Dahl
Research Paper
Rodents
Salts
Sodium
Sodium channels
Sodium Chloride, Dietary - pharmacology
Themed Section: Research Papers
Vasodilation
Vasodilation - drug effects
Veins & arteries
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Summary:Background and Purpose Our recent studies show that the reduced activity of epithelial sodium channels (ENaC) in endothelial cells accounts for the adaptation of vasculature to salt in Sprague–Dawley rats. The present study examines a hypothesis that enhanced ENaC activity mediates the loss of vasorelaxation in Dahl salt‐sensitive (SS) rats. Experimental Approach We used the cell‐attached patch‐clamp technique to record ENaC activity in split‐open mesenteric arteries. Western blot and immunofluorescence staining were used to evaluate the levels of aldosterone, ENaC, eNOS and NO. Blood pressure was measured with the tail‐cuff method and the artery relaxation was measured with the wire myograph assay. Key Results High‐salt (HS) diet significantly increased plasma aldosterone and ENaC activity in the endothelial cells of Dahl SS rats. The endothelium‐dependent artery relaxation was blunted by HS challenge in these rats. Amiloride, a potent blocker of ENaC, increased both phosphorylated eNOS and NO and therefore prevented the HS‐induced loss of vasorelaxation. As, in SS rats, endogenous aldosterone was already elevated by HS challenge, exogenous aldosterone did not further elevate ENaC activity in the rats fed with HS. Eplerenone, a mineralocorticoid receptor antagonist, attenuated the effects of HS on both ENaC activity and artery relaxation. Conclusions and Implications These data suggest that HS diet blunts artery relaxation and causes hypertension via a pathway associated with aldosterone‐dependent activation of ENaC in endothelial cells. This pathway provides one of the mechanisms by which HS causes hypertension in Dahl SS rats. Linked Articles This article is part of a themed section on Spotlight on Small Molecules in Cardiovascular Diseases. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v175.8/issuetoc
ISSN:0007-1188
1476-5381
DOI:10.1111/bph.13817