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B Activation and TNF
Up-regulation Correlate with Salt-sensitive Hypertension in Dahl Salt-sensitive (SS) Rats
1 Physiology and Biophysics, University of Mississippi Medical Center, Jackson, Mississippi, United States
* To whom correspondence should be addressed. E-mail: jgu{at}physiology.umsmed.edu.
Molecular mechanisms of salt-sensitive hypertension related to renal inflammation have not been defined. We seek to determine whether a high salt diet induces renal activation of NF
B and up-regulation of TNF
related to the development of hypertension in Dahl SS rats. Six, 8-wk-old male Dahl SS rats received a high sodium diet (HS, 4%) and 6 Dahl SS rats received a low sodium diet (LS, 0.3 %) for 5 weeks. In the end, mean arterial pressure (MAP) was determined in conscious rats by continuous monitoring through a catheter placed in the carotid artery. MAP was significantly higher in the HS than the LS group (177.9±3.7 vs. 109.4±2.9 mmHg, P<0.001). There was a significant increase in urinary albumin secretion in the HS group, compared to the LS group (22.3 ±2.6 vs. 6.1±0.7 mg/d; P<0.001). Electrophoretic mobility shift assay (EMSA) demonstrated that the binding activity of NF
B p65 proteins in the kidneys of Dahl SS rats were significantly increased by 53% in the HS group, compared to the LS group (P=0.007). ELISA indicated that renal protein levels of TNF
, but not IL-6,
interferon-
, and CCL28, were significantly higher in the HS than the LS group (2.3±0.8 vs. 0.7±0.2 pg/mg; P=0.036). We demonstrated that plasma levels of TNF
were significantly increased by 5-fold in Dahl SS rats on a high salt diet, compared to a low salt diet. Also, we found that increased physiologically relevant sodium concentration (10 mmol/L) directly stimulated NF
B activation in cultured human renal proximal tubular epithelial cells. These findings support the hypothesis that activation of NF
B and up-regulation of TNF
are the important renal mechanisms linking pro-inflammatory response to salt-sensitive hypertension.
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