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HEMODYNAMICS AND CARDIORENAL INTEGRATION

Tetradecylthioacetic acid downregulates cyclooxygenase 2 in the renal cortex of two-kidney, one-clip hypertensive rats

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

Submitted 27 November 2007 ; accepted in final form 1 October 2008

The effect of tetradecylthioacetic acid (TTA) on the cyclooxygenase (COX) system was investigated in two-kidney, one-clip (2K1C) hypertensive rats. The systolic blood pressure (BP) was increased 6 wk after clipping to 183 ± 4 vs.127 ± 3 mmHg in TTA-treated 2K1C rats. The COX1 protein expression was not affected either by the 2K1C procedure or by TTA treatment. COX2 expression was upregulated in both kidneys, but to a greater extent in the clipped kidney. COX2 activity was 16 ± 3% in control and 38 ± 2% (P < 0.001) in the clipped kidney, and COX2 protein expression was 1.3 ± 0.04 in control and 1.6 ± 0.12 in the clipped kidney (P = 0.006). TTA reduced COX2 activity to control levels. Subcutaneously infusion of a COX2 inhibitor did not reduce BP. Peroxisome proliferator-activated receptors (PPARs) were detected in both kidneys, and PPAR was upregulated in the nonclipped kidney after TTA treatment. PGE₂ in renal cortex was increased in 2K1C (31 ± 0.3 in the clipped and 28 ± 0.2 pg/ml nonclipped kidney, P < 0.001 compared with control). TTA lowered the PGE₂ to control levels. Renal blood flow (RBF) response to exogenous ANG II injected in the control and nonclipped kidney was exaggerated after indomethacin treatment but unchanged in the nonclipped kidney of the K1C TTA group. Overall, these results indicate that, after 6 wk of treatment, TTA downregulated the COX2 activity, which have potentially important effects on the regulation of renal hemodynamics but does not explain TTAs ability to lower BP.

cyclooxygenase; renal blood flow; angiotensin II; prostaglandin E₂