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RENAL HEMODYNAMICS AND CARDIORENAL INTEGRATION

Tetradecylthioacetic acid prevents the inflammatory response in two-kidney, one-clip hypertension

¹Renal Research Group and ²Lipid Research Group, Institute of Medicine, University of Bergen, and ³Haukeland University Hospital, Bergen, Norway

Submitted 16 August 2007 ; accepted in final form 15 November 2007

ANG II promotes inflammation through nuclear factor-B (NF-B)-mediated induction of cytokines and reactive oxygen species (ROS). The aim of the present study was to examine the effect of tetradecylthioacetic acid (TTA), a modified fatty acid, on NF-B, proinflammatory markers, ROS, and nitric oxide (NO) production in two-kidney, one-clip (2K1C) hypertension. The 2K1C TTA-treated group had lower blood pressure (128 ± 3 mmHg) compared with 2K1C nontreated (178 ± 5 mmHg, P < 0.001). The p50 and p65 subunits of NF-B were higher in the clipped kidney (0.44 ± 0.01 and 0.22 ± 0.01, respectively) compared with controls (0.25 ± 0.03 and 0.12 ± 0.02, respectively, P < 0.001). In the 2K1C TTA-treated group, these values were similar to control levels. The same pattern of response was seen in the nonclipped kidney. In 2K1C hypertension, cytokines plasma were higher than in control: TNF- was 13.5 ± 2 pg/ml (P < 0.03), IL-1β was 58.8 ± 10 pg/ml (P = 0.003), IL-6 was 210 ± 33 pg/ml (P < 0.001), and monocyte chemoattractant protein-1 was 429 ± 21 pg/ml (P = 0.04). In the 2K1C TTA-treated group, these values were similar to controls, and the same pattern was seen in the clipped kidney. Clipping increased 8-iso-PGF-2 (P < 0.01) and decreased NO production (P < 0.01 vs. control) in the urine. TTA treatment normalized these values. NO production was also lower in clipped and nonclipped kidney (P < 0.001). After TTA treatment, these values were similar to controls. The results indicate that TTA has a potent anti-inflammatory effect in 2K1C by inhibition of p50/p65 NF-B subunit activation, reduction of cytokines production and ROS, and enhanced NO production.

nuclear factor-B; cytokines; reactive oxygen species; nitric oxide

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				L. M. Bivol, M. Hultstrom, O. A. Gudbrandsen, R. K. Berge, and B. M. Iversen Tetradecylthioacetic acid downregulates cyclooxygenase 2 in the renal cortex of two-kidney, one-clip hypertensive rats Am J Physiol Regulatory Integrative Comp Physiol, December 1, 2008; 295(6): R1866 - R1873. [Abstract] [Full Text] [PDF]