Previous studies performed in our laboratory using dogs, rats and mice have demonstrated that inhibition of nitric oxide (NO) increases superoxide activity in the kidney and this imbalance enhances tubular sodium reabsorption leading to salt retention and the development of salt sensitive hypertension. However, recent findings in our laboratory also show that systemic NO inhibition results in an increase in tumor necrosis factor-alpha (TNF-α; a pro-inflammatory cytokine) and a decrease in interleukin-10 (IL-10; an anti-inflammatory cytokine) levels in plasma and in renal tissue which are associated with marked infiltration of macrophages in the kidneys. As these cytokines are suggested to be involved in the pathophysiology of salt-sensitive hypertension, we examined the hypothesis that high salt (HS) intake in NO deficient condition enhances the production of pro-inflammatory cytokines in the kidney. Using appropriate ELISA kits, the levels of different cytokines (pro-inflammatory, TNF-α, and IL-6 and anti-inflammatory, IL-10) were measured in plasma and renal tissues collected from wild type (WT; C57BL6) and eNOS enzyme knockout (eNOS-KO) mice (~8 wks old) which were fed either normal (NS) or HS (4% NaCl) containing diet for 2 weeks. Mean systemic blood pressure (measured by tail-cuff plethysmography) was significantly increased in eNOS KO (111±4 to 136±8 mmHg) but not in WT (99±5 to107±4 mmHg) due to HS intake. The changes in cytokines levels are summarized in the Table 1. The plasma level of TNF-α remains undetected in both WT & eNOS KO mice during NS intake but showed a slight increased during HS intake. During NS intake, the plasma level of IL-6 was higher and that of IL-10 was lower in eNOS KO mice compared to WT mice. However, compared to the values during NS intake, all the renal levels of cytokines were lower in the kidney during HS intake both in WT as well as eNOS KO mice. These findings indicate that HS intake generally suppresses the levels of both anti- as well as pro-inflammatory cytokines, particularly in the kidney. These data suggest that NO inhibition induced by deficient activity of eNOS enzyme generally responsible for upregulation of inflammatory cytokines in the kidney.