Submitted on November 27, 2007
Accepted on October 1, 2008
Tetradecylthioacetic acid down-regulates cyclooxygenase 2 in the renal cortex of two-kidney, one-clip hypertensive rats
Liliana Monica Bivol1, Michael Hultstrom2, Oddrun A. Gudbrandsen3, Rolf Kristian Berge1, and Bjarne Magnus Iversen1*
1 Institute of Medicine, University of Bergen, Bergen, Norway
2 Renal Research Group, Institute of Medicine, University of Bergen, Bergen, Norway
3 Lipid Research Group, Institute of Medicine, University of Bergen, Bergen, Norway
* To whom correspondence should be addressed. E-mail: bjarne.iversen{at}med.uib.no.
The effect of tetradecylthioacetic acid (TTA) on the cyclooxygenase (COX) system was investigated in 2K1C hypertensive rats. The systolic blood pressure (BP) was increased 6 weeks after clipping to 183 ± 4 mmHg 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 up-regulated 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 delta was up-regulated in the non-clipped kidney after TTA treatment. Prostaglandin E2 (PGE2) in renal cortex was increased in 2K1C (31 ±0.3 in the clipped and 28 ±0.2 pg·ml-1 non-clipped kidney, p<0.001 compared to control). TTA lowered the PGE2 to control level. Renal blood flow (RBF) response to exogenous angiotensin II (ANG II) injected into the control and non-clipped kidney was exaggerated after indomethacin treatment, but unchanged in the non-clipped kidney of 2K1C TTA group. Overall, these results indicate that after 6 weeks of treatment, TTA down-regulated COX2 activity, which have potentially important effects on the regulation of renal hemodynamics but does not explain TTAs ability to lower blood pressure
