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

Abstract

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.

Anti-inflammatory effects of tetradecylthioacetic acid (TTA) in macrophage-like cells from Atlantic salmon (Salmo salar L.)

“…Moreover, KLF11 an inhibitor of cellular PGE 2 synthesis [23] and APOEB, the teleost homolog to apoE, was found to be strongly up-regulated. PGE 2 is an important mediator of inflammation and has been previously reported to be down-regulated in response to TTA treatment [12,24]. ApoE secreted by macrophages participates in the regulation of cholesterol efflux, reducing the cholesterol-ester accumulation in macrophages attached to the arterial wall [25].…”

Soluble epoxide hydrolase in the generation and maintenance of high blood pressure in spontaneously hypertensive rats

“…Many of these can be viewed as being secondary to BP reduction, such as increases in some EpOMEs and EETs, 9,12,13-TriHOME, and 20-HETE, and decreases in several prostaglandins (PGE 2 , PGD 2 , 6-keto-PGF1␣, PGJ2) and 8-HETE. Decreases in renal prostaglandins and urinary prostaglandin excretion often accompany BP reduction in other rodent models of hypertension (2,4,29) and are probably not specific for SEH inhibition. Indeed, in 12-wk SHR without BP reduction, SEH inhibition increased 9,12,13-TriHOME, quite the reverse effect.…”

Distinct Roles of Central and Peripheral Prostaglandin E2 and EP Subtypes in Blood Pressure Regulation

“…65 In two kidneys, one clip hypertensive (2K1C) rats, COX-2 was upregulated in both kidney, but to a greater extent in the clipped kidney. 66 Moreover, COX-2 deletion or COX-2 inhibitors reduce renin secretion in response to maneuvers including low-salt intake, angiotensin-converting enzyme inhibition, angiotensin AT1 receptor antagonism, and reduced renal perfusion pressure. [67][68][69][70][71][72] However, functional studies using COX-2 inhibitors in 2K1C hypertensive rats have yield conflicting results.…”