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This Article Full Text Full Text (PDF) All Versions of this Article: 294/2/R438    most recent 00590.2007v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Google Scholar Articles by Bivol, L. M. Articles by Iversen, B. M. PubMed PubMed Citation Articles by Bivol, L. M. Articles by Iversen, B. M.

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