Influence of indomethacin on the haemodynamic effects of lipopolysaccharide in rats

Fatehi‐Hassanabad, Zahra; Müller, B; Andriantsitohaina, Ramaroson; Furman, Brian L.; Parratt, J. R.; Stoclet, Jean‐Claude

doi:10.1111/j.1472-8206.1996.tb00304.x

Cited by 10 publications

(5 citation statements)

References 19 publications

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“…The beneficial effects of indomethacin are correlated with decreased levels of nitrite and prostaglandins in biological fluids from endotoxemic rats (Futaki et al , 1997). Indomethacin has also shown to abolish or significantly attenuate the decrease in blood pressure (Fatehi-Hassanabad et al , 1996) or have no significant effect on blood pressure in endotoxemic rats (Pique et al , 1988; Vayssettes-Courchay et al , 2002). Vasoconstriction and increased blood pressure after systemic inhibition of NOS results not only from withdrawal of vasodilator NO, but from increased activity of the vasoconstrictor systems, including sympathetic nervous and renin-angiotensin systems, and production of endothelins and 20-hydroxyeicosatetraenoic acid (20-HETE), an arachidonic acid metabolite derived via cytochrome P450 (CYP) (Fleming, 2001; Roman, 2002; Zatz and Baylis, 1998).…”

Section: Introductionmentioning

confidence: 99%

Prostaglandins inhibit cytochrome P450 4A activity and contribute to endotoxin-induced hypotension in rats via nitric oxide production

et al. 2008

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Increased production of nitric oxide (NO) and prostaglandins contribute to development of hypotension during endotoxemia. We have previously demonstrated that endotoxemia-induced increase in NO production suppresses renal cytochrome P450 (CYP) 4A expression and activity, and that selective inhibition of inducible NO synthase (iNOS) with 1,3-PBIT restores renal CYP 4A protein and activity and mean arterial pressure (MAP). By using cyclooxygenase (COX) inhibitor indomethacin, we investigated herein whether prostaglandins, via NO production, inhibit renal CYP 4A1 protein expression and CYP 4A activity and contribute to the endotoxin-induced hypotension. In conscious male Sprague-Dawley rats, endotoxin (10 mg/kg, intraperitoneal (i.p.)) reduced MAP, increased serum nitrite and bicyclo PGE 2 levels, renal nitrite production and iNOS protein expression, and decreased renal CYP 4A1 protein expression and CYP 4A activity after 4 h injection. All of the endotoxin-induced changes, except for increase in renal nitrite production, were prevented by indomethacin (5 mg/kg, i.p. 1 h after endotoxin). The effects of indomethacin on the endotoxininduced decrease in MAP, CYP 4A1 protein expression and CYP 4A activity were minimized by the CYP 4A inhibitor, aminobenzotriazole (50 mg/kg, i.p. 1 h after endotoxin). These data suggest that prostaglandins produced during endotoxemia increase iNOS protein expression and NO synthesis, and decrease CYP 4A protein expression and CYP 4A activity and that inhibition of iNOS or COX restores renal CYP 4A protein level and CYP 4A activity and MAP presumably due to increased production of arachidonic acid metabolites derived from CYP 4A.

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Section: Introductionmentioning

confidence: 99%

Prostaglandins inhibit cytochrome P450 4A activity and contribute to endotoxin-induced hypotension in rats via nitric oxide production

et al. 2008

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“…Endotoxin is known to induce the expression of other enzymes, including cyclo‐oxygenase (COX‐2) ( Bishop‐Bailey et al ., 1997 ) suggesting that additional mechanisms are likely to contribute to endotoxin‐induced changes in vascular reactivity. For example, increased prostanoid production and enhanced potassium channel activity have been reported to contribute to the development of hypotension and vascular hyporeactivity ( Wu et al ., 1995b ; Fatehi‐Hassanabad et al ., 1996 ; Clapp & Tinker, 1998 ).…”

Section: Introductionmentioning

confidence: 99%

Temporal variation in endotoxin‐induced vascular hyporeactivity in a rat mesenteric artery organ culture model

O’Brien

Wilson

Sibbald

et al. 2001

British J Pharmacology

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1 Endotoxin-induced vascular hyporeactivity to phenylephrine (PE) is well described in rodent aorta, but has not been investigated in smaller vessels in vitro. 2 Segments of rat superior mesenteric artery were incubated in culture medium with or without foetal bovine serum (10%) for 6, 20 or 46 h in the presence or absence of bacterial lipopolysaccharide (LPS; 1 ± 100 mg ml 71 ). 3 Contractions to PE were measured with or without nitric oxide synthase (NOS) inhibitors: L-NAME (300 mM), aminoguanidine (AMG; 400 mM) 1400W (10 mM) and GW273629 (10 mM); the guanylyl cyclase inhibitor, ODQ (3 mM); the COX-2 inhibitor, NS-398 (10 mM). Contractile responses to the thromboxane A 2 mimetic, U46619 were also assessed. 4 In the presence of serum, LPS induced hyporeactivity at all time points. In its absence, hyporeactivity only occurred at 6 and 20 h. 5 L-NAME and AMG fully reversed hyporeactivity at 6 h, whereas they were only partially e ective at 20 h and not at all at 46 h. In contrast partial reversal of peak contraction was observed with 1400W (62% at 46 h), GW273629 (57% at 46 h) and ODQ (75% at 46 h). COX-2 inhibition produced no reversal. 6 In contrast to PE, contractions to U46619 were substantially less a ected by LPS. 7 We describe a well-characterized reproducible model of LPS-induced hyporeactivity, which is largely mediated by the NO-cyclic GMP-dependent pathway. Importantly, long-term (2-day) production of NO via iNOS is demonstrated. Moreover, conventional doses of L-NAME and AMG became increasingly ine ective over time. Thus, the choice of inhibitor merits careful consideration in long-term models.

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“…The beneficial effects of indomethacin are correlated with decreased levels of nitrite and prostanoids in biological fluids from endotoxaemic rats [40]. Indomethacin also abolishes or significantly attenuates the decrease in mean arterial pressure (MAP) [41] or has no significant effect on blood pressure in endotoxaemic rats [42]. Our previous studies suggested that dual inhibition of iNOS and COX by indomethacin restores MAP presumably because of increased production of 20‐HETE derived from AA by CYP4A in endotoxaemic rats [32].…”

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confidence: 99%

Piroxicam Reverses Endotoxin‐Induced Hypotension in Rats: Contribution of Vasoactive Eicosanoids and Nitric Oxide

Buharalioğlu¹,

Korkmaz²,

Cuez³

et al. 2011

Basic Clin Pharma Tox

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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 due to 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 PGI2, PGE2, 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-PGF1α and PGE2 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.

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Influence of indomethacin on the haemodynamic effects of lipopolysaccharide in rats

Cited by 10 publications

References 19 publications

Prostaglandins inhibit cytochrome P450 4A activity and contribute to endotoxin-induced hypotension in rats via nitric oxide production

Prostaglandins inhibit cytochrome P450 4A activity and contribute to endotoxin-induced hypotension in rats via nitric oxide production

Temporal variation in endotoxin‐induced vascular hyporeactivity in a rat mesenteric artery organ culture model

Piroxicam Reverses Endotoxin‐Induced Hypotension in Rats: Contribution of Vasoactive Eicosanoids and Nitric Oxide

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