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- W1455931046 abstract "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/mm2) 1.7±0.4 1.1±0.3 1.9±0.3 2.9±0.9 SPAK (ODU/mm2) 5.9±0.1 0.8±0.3 * 6.4±1.5 ≠ 7.34±1.5 τ OxSR1 (ODU/mm2) 6.7±1.8 3.9±1.6 12.7±2.7 11.6±2.3 DSR 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/mm2) 1.2±0.3 0.5±0.01 2.4±0.8 2.9±0.4 τ SPAK (ODU/mm2) 2.42±1 0.7±0.2 * 4.2±1.6 4.17±0.6 OxSR1 (ODU/mm2) 2.2±0.6 1±0.2 11.2±4.5 11.4±2.7 Significance 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." @default.
- W1455931046 created "2016-06-24" @default.
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- W1455931046 date "2015-04-01" @default.
- W1455931046 modified "2023-10-16" @default.
- W1455931046 title "Impaired Regulation of the Renal Sodium Chloride Cotransporter (NCC) in Animal Models of Salt‐Sensitive Hypertension" @default.
- W1455931046 doi "https://doi.org/10.1096/fasebj.29.1_supplement.811.2" @default.
- W1455931046 hasPublicationYear "2015" @default.
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