Tetradecylthioacetic acid downregulates cyclooxygenase 2 in the renal cortex of two-kidney, one-clip hypertensive rats.
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 PPARdelta 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.
Renal Research Group, Institute of Medicine, University of Bergen, Bergen, Norway.
Liliana Monica
LM
Bivol
Michael
M
Hultström
Oddrun A
OA
Gudbrandsen
Rolf K
RK
Berge
Bjarne M
BM
Iversen
D000284:Administration, Oral; D000804:Angiotensin II / Q000008:administration & dosage; D000818:Animals; D000959:Antihypertensive Agents / Q000008:administration & dosage / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects; D003250:Constriction; D051545:Cyclooxygenase 1 / Q000378:metabolism; D051546:Cyclooxygenase 2 / Q000378:metabolism*; D052246:Cyclooxygenase 2 Inhibitors / Q000008:administration & dosage / Q000494:pharmacology*; D015232:Dinoprostone / Q000652:urine; D004195:Disease Models, Animal; D015536:Down-Regulation; D006978:Hypertension, Renovascular / Q000188:drug therapy* / Q000201:enzymology / Q000209:etiology / Q000503:physiopathology; D055104:Infusions, Subcutaneous; D007269:Injections, Intra-Arterial; D007672:Kidney Cortex / Q000187:drug effects* / Q000201:enzymology / Q000503:physiopathology; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism; D047492:Peroxisome Proliferator-Activated Receptors / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D012077:Renal Artery / Q000601:surgery; D012079:Renal Circulation / Q000187:drug effects; D013440:Sulfides / Q000008:administration & dosage / Q000494:pharmacology*; D013997:Time Factors
D000959:Antihypertensive Agents; D052246:Cyclooxygenase 2 Inhibitors; D008565:Membrane Proteins; D047492:Peroxisome Proliferator-Activated Receptors; D013440:Sulfides; D000804:Angiotensin II; C062078:1-(carboxymethylthio)tetradecane; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; C496513:Ptgs1 protein, rat; C489691:Ptgs2 protein, rat; D015232:Dinoprostone