ANG II promotes inflammation through nuclear factor kappa beta (NF-kB) mediated induction of cytokines and radical oxidants

ANG II promotes inflammation through nuclear factor kappa beta (NF-kB) mediated induction of cytokines and radical oxidants species (ROS). The aim of the present study was to examine the effect of TTA, a modified fatty acid, on NF-kB, pro-inflammatory markers, ROS and nitric oxide (NO) production in 2K1C hypertension. 2K1C TTA treated group had lower blood pressure (128 ± 3 mmHg) compared to 2K1C non-treated (178 ± 5 mmHg, p<0.001). The p50 and p65 subunits of NF-kB were higher in the clipped kidney (0.44 ± 0.01 and 0.22 ± 0.01) compared to controls (0.25 ± 0.03 and 0.12 ± 0.02, p<0.001). In 2K1C TTA-treated group these values were similar to control levels. The same pattern of response was seen in the non-clipped kidney. In 2K1C hypertension, cytokines plasma were higher than in 210 ± 33 pgml-1 (p<0.001) and MCP-1 was 429 ± 21 pg. ml-1 (p=0.04). In 2K1C TTA-treated group, these values were similar to controls and the same pattern was seen in the clipped kidney. Clipping increased 8-iso-PGF2 (p<0.01) and decreased NO production (p<0.01 versus control) in the urine. TTA treatment normalized these values. NO production was also lower in clipped and non-clipped kidney (p<0.001).After TTA treatment these values were similar to controls. The results indicate that TTA has potent anti-inflammatory effect in 2K1C by inhibition of p50/p65 NF-kB subunits activation, by reduction of cytokines production and ROS, and enhanced NO production.