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Impaired Regulation of the Renal Sodium Chloride Cotransporter (NCC) in Animal Models of Salt‐Sensitive Hypertension
Author(s) -
Walsh Kathryn,
Wainford Richard
Publication year - 2015
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.29.1_supplement.811.2
Subject(s) - cotransporter , sodium , medicine , endocrinology , chemistry , chloride , organic chemistry
Aim These studies test the hypothesis that excess norepinephrine (NE) and a high salt intake impairs renal NCC regulation evoking salt‐sensitive hypertension. Methods: Sprague‐Dawley (SD) rats receiving a s.c. saline or NE (600ng/min) infusion were fed a 0.4% (NS) or 8% NaCl (HS) diet for 14 days. Naïve Dahl Salt‐Resistant (DSR) and Dahl Salt‐Sensitive (DSS) rats were placed on a NS or HS diet for 21 days. Immunoblotting for NCC, STE‐20 Alanine/Proline kinase (SPAK), and oxidative stress response‐1 (OxSR1) was performed on kidney cortex tissue and normalized to β‐actin (N=5/6). Results: Salt‐resistant phenotypes (saline‐infusion & DSR) show dietary sodium evoked suppression of NCC. Salt‐sensitive phenotypes (NE‐infusion & DSS) fail to suppress NCC expression on a high salt diet. Dietary sodium evoked suppression of SPAK was observed in salt‐resistant phenotypes and this was prevented in salt‐sensitive phenotypes. A high salt diet did not alter OxSR1 expression but, salt‐resistant phenotypes have lower endogenous levels of OxSR1 than salt‐sensitive phenotypes.s.c Saline s.c Saline s.c. NE s.c. NE Type of Diet NS HS NS HS MAP (mmHg) 124±2 124±1 151±3 τ 171±4 *τ Plasma NE (nmol/L n.d. n.d. 99±3 125±20 NCC (ODU/mm 2 ) 1.7±0.4 1.1±0.3 1.9±0.3 2.9±0.9 SPAK (ODU/mm 2 ) 5.9±0.1 0.8±0.3 * 6.4±1.5 ≠ 7.34±1.5 τ OxSR1 (ODU/mm 2 ) 6.7±1.8 3.9±1.6 12.7±2.7 11.6±2.3DSR DSR DSS DSS Type of Diet NS HS NS HS MAP (mmHg) 129±3 131±2 138±6 166±6 * Plasma NE (nmol/L) 48±6 29±4 47±6 76±4 τ NCC (ODU/mm 2 ) 1.2±0.3 0.5±0.01 2.4±0.8 2.9±0.4 τ SPAK (ODU/mm 2 ) 2.42±1 0.7±0.2 * 4.2±1.6 4.17±0.6 OxSR1 (ODU/mm 2 ) 2.2±0.6 1±0.2 11.2±4.5 11.4±2.7Significance symbols:*p<0.05 vs. resp. NS gp; τp<0.05 vs. resp. control gp; ≠p<0.05 vs. resp. control + HS gp Conclusion These data support an interaction of increased dietary salt intake and excess NE in the dysregulation of the NCC to drive the development of salt‐sensitive hypertension. Our findings suggest that NCC dysregulation may depend on impaired upstream dietary sodium evoked suppression of SPAK and an underlying phenotypic difference in endogenous OxSR1 levels.