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Renal Activation of NF κ B and Up‐regulation of TNF α Correlate with Salt‐sensitive Hypertension in Dahl SS Rats
Author(s) -
Gu JianWei,
Tian Niu,
Shparago Megan,
Tan Wei,
Bailey Amelia Purser,
Manning R. Davis
Publication year - 2006
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.20.4.a336-b
Subject(s) - tumor necrosis factor alpha , nf κb , medicine , salt (chemistry) , endocrinology , chemistry , inflammation
Recent evidence suggests that a renal pro‐inflammatory response plays an important role in salt sensitive hypertension. However, the molecular mechanisms of dietary salt‐induced hypertension are poorly understood. We seek to determine whether a high salt diet induces renal activation of NF κ B and up‐regulation of TNF α related to the development of hypertension in Dahl SS rats. Four, 8‐wk‐old male Dahl SS rats received a high sodium diet (HS, 4%) and 4 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). Total tissue protein or nuclear protein was extracted from the whole kidneys. Electrophoretic mobility shift assay (EMSA) demonstrated that the binding activity of NF κ B p65 proteins in the kidneys of Dahl SS rats were significantly increased by 45% in the HS group, compared to the LS group (P=0.007). ELISA indicated that renal protein levels of TNF α were significantly higher in the HS than the LS group (2.3±0.8 vs. 0.7±0.2 pg/mg; P=0.036). The results show that a high salt diet induces the activation of NF κ B and TNF α protein expression in the kidneys of Dahl SS rats in relation to the development of hypertension and renal injury. These findings support the hypothesis that NF κ B and TNF α may be the key renal pro‐inflammatory factors in mediating salt sensitive hypertension. (NIH/HL51971 & NIH/AA013821)