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Role of the epithelial sodium channel (ENaC) in the development of salt‐sensitive hypertension
Author(s) -
Pavlov Tengis S.,
Levchenko Vladislav,
Ilatovskaya Daria V.,
O'Connor Paul M.,
Cowley Allen W.,
Staruschenko Alexander
Publication year - 2012
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.26.1_supplement.867.8
Subject(s) - epithelial sodium channel , amiloride , endocrinology , medicine , chemistry , sodium , reabsorption , aldosterone , downregulation and upregulation , renin–angiotensin system , nephron , renal sodium reabsorption , kidney , blood pressure , biology , biochemistry , gene , organic chemistry
Dahl salt‐sensitive (SS) rats fed a high salt diet exhibit increased blood pressure and renal damage compared with SS rats fed a low salt diet and consomic, salt‐resistant SS‐13 BN rats. Amiloride‐sensitive sodium entry, via ENaC, is the rate‐limiting step for Na + absorption in the aldosterone sensitive distal nephron (ASDN). Previous studies reported that the handling of salt and water in the kidney of SS rats is defective and these defects are mediated by enhanced Na + reabsorption in the TAL of the loop of Henle. The contribution of ENaC‐mediated pathways in the ASDN in the development of salt‐sensitive hypertension is poorly understood. Initially we studied an effect of ENaC inhibitors on MAP in vivo . Benzamil, given through drinking water (15 mg/L), and amiloride given i/v (6 mg/kg/day) preclude the development of hypertension in SS rats. Western blotting and immunohistochemistry demonstrate that expression of ENaC subunits is increased in SS rats fed a high salt diet compared to SS rats fed a low salt diet and SS‐13 BN rats. Patch clamp analysis of ENaC activity in split opened tubules also demonstrated upregulation of ENaC activity in SS rats fed a high salt diet compared to control SS and consomic SS‐13 BN rats. Thus, we hypothesize that ENaC is upregulated in SS rats fed a high salt diet and that ENaC‐mediated sodium absorption in the ASDN is of critical importance in the development of salt‐sensitive hypertension.