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• W1544480516 abstract "Abstract: Nitric oxide (NO) produced by inducible NO synthase (iNOS) is responsible for endotoxin‐induced vascular hyporeactivity and hypotension resulting in multiple organ failure. Endotoxic shock is also characterized by decreased expression of constitutive cyclooxygenase (COX‐1), cytochrome P450 (CYP) 4A and endothelial NOS (eNOS). Our previous studies demonstrated that dual inhibition of iNOS and COX with a selective COX‐2 inhibitor, NS‐398, or a non‐selective COX inhibitor, indomethacin, restores blood pressure presumably because of increased production of 20‐hydroxyeicosatetraenoic acid (20‐HETE) derived from arachidonic acid (AA) by CYP4A in endotoxaemic rats. The aim of this study was to investigate the effects of piroxicam, a preferential COX‐1 inhibitor, on the endotoxin‐induced changes in blood pressure, expression of COX‐1, inducible COX (COX‐2), CYP4A1, eNOS, iNOS and heat shock protein 90 (hsp90), and production of PGI 2 , PGE 2 , 20‐HETE and NO. Injection of endotoxin (10 mg/kg, i.p.) to male Wistar rats caused a fall in blood pressure and an increase in heart rate associated with elevated renal 6‐keto‐PGF 1α and PGE 2 levels as well as an increase in COX‐2 protein expression. Endotoxin also caused an elevation in systemic and renal nitrite levels associated with increased renal iNOS protein expression. In contrast, systemic and renal 20‐HETE levels and renal expression of eNOS, COX‐1 and CYP4A1 were decreased in endotoxaemic rats. The effects of endotoxin, except for renal COX‐1 and eNOS protein expression, were prevented by piroxicam (10 mg/kg, i.p.), given 1 hr after injection of endotoxin. Endotoxin did not change renal hsp90 protein expression. These data suggest that a decrease in the expression and activity of COX‐2 and iNOS associated with an increase in CYP4A1 expression and 20‐HETE synthesis contributes to the effect of piroxicam to prevent the hypotension during rat endotoxaemia." @default.
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• W1544480516 date "2011-05-06" @default.
• W1544480516 modified "2023-10-16" @default.
• W1544480516 title "Piroxicam Reverses Endotoxin-Induced Hypotension in Rats: Contribution of Vasoactive Eicosanoids and Nitric Oxide" @default.
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• W1544480516 doi "https://doi.org/10.1111/j.1742-7843.2011.00708.x" @default.
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