The effects of selective and nonselective cyclooxygenase inhibitors on endothelin-1-induced fever in rats

American Journal of Physiology - Regulatory Integrative and Comparative Physiology - Tập 288 Số 3 - Trang R671-R677 - 2005
Aline S.C. Fabricio1, Fabiane H Veiga, Rodrigo Cristofoletti, Pierluigi Navarra, Fabiane H. Veiga-Souza
1Institute of Pharmacology, Catholic University Medical School, Largo Francesco Vito 1, 00168 Rome, Italy

Tóm tắt

It was previously shown that sustained fever can be induced in rats by central injection of endothelin-1 (ET-1). This peptide appears to participate in the mechanism(s) of LPS-induced fever, which is reduced by pretreatments with ETB receptor antagonists. In this study, we compared the effects of a nonselective cyclooxygenase (COX) inhibitor, indomethacin, with those of two selective COX-2 inhibitors, celecoxib and lumiracoxib, on ET-1-induced fever in rats. Fever induced in conscious animals by ET-1 (1 pmol icv) or LPS (5 μg/kg iv) was prevented by pretreatments with celecoxib (5 and 10 mg/kg) or lumiracoxib (5 mg/kg) given by oral gavage 1 h before stimuli. Lower doses of celecoxib had partial (2.5 mg/kg) or no effect (1 mg/kg). Indomethacin (2 mg/kg ip) partially inhibited fever induced by LPS but had no effect on ET-1-induced fever. The levels of PGE2 and PGF2α in the cerebrospinal fluid (CSF) of pentobarbital sodium-anesthetized rats were significantly increased 3 h after the injection of LPS or ET-1. The latter increase was abolished by celecoxib at all tested doses and by indomethacin. In conclusion, selective COX-2 inhibitors were able to prevent ET-1-induced fever, indicating a role for COX-2 in this phenomenon. However, the fact that reduced CSF PG levels obtained with indomethacin and a low dose of celecoxib are not accompanied by changes in fever induced by ET-1, along with the lack of inhibitory effects of indomethacin on ET-1 fever, suggests that the latter might also involve COX-2-independent mechanisms.

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Tài liệu tham khảo

10.1002/cne.903550208

10.1016/S0149-7634(97)00051-1

10.1523/JNEUROSCI.19-02-00716.1999

10.1046/j.0953-816x.2001.01551.x

10.1016/S0169-328X(98)00025-4

10.1152/ajpregu.1997.272.6.R1712

10.1016/0006-8993(96)00575-6

10.1177/039463200301600107

Coceani F, Lees J, and Bishai I. Further evidence implicating prostaglandin E2 in the genesis of pyrogen fever. Am J Physiol 23: R463–R469, 1988.

10.1152/ajpregu.1995.269.3.R527

10.1016/S1385-299X(99)00062-8

10.1007/s004240100572

10.1007/PL00000278

10.1002/(SICI)1096-9861(19970505)381:2<119::AID-CNE1>3.0.CO;2-6

10.1038/sj.bjp.0702075

10.1007/s002210050734

10.1016/0031-9384(90)90025-Y

10.1097/00005344-200036051-00026

10.1016/S0168-0102(02)00083-4

Institute for Laboratory Animal Research. National Research Council. Guide for the Care and Use of Laboratory Animals. Washington, DC: National Academy Press, 1996.

10.1152/ajpregu.00347.2002

10.1152/ajpregu.00570.2002

10.1152/ajpendo.1992.262.2.E246

Koyama Y., Mizobata T., Yamamoto N., Hashimoto H., Matsuda T., and Baba A. Endothelins stimulate expression of cyclooxygenase 2 in rat cultured astrocytes. J Neurochem 73: 1004–1011, 1999.

10.1046/j.1471-4159.1998.70020452.x

10.1016/S0006-8993(99)01225-1

10.1152/ajpregu.00200.2002

10.1124/dmd.32.5.566

10.1016/j.tips.2004.02.008

10.1523/JNEUROSCI.18-16-06279.1998

10.1016/0091-3057(91)90223-O

10.1097/00005072-199911000-00008

10.1523/JNEUROSCI.22-11-04600.2002

10.1016/0090-6980(91)90051-G

10.1002/1096-9861(20001204)428:1<20::AID-CNE3>3.0.CO;2-X

Paxinos G and Watson C. The Rat Brain in Stereotaxic Coordinates. New York: Academic Press, 1986.

10.1007/s004240100718

10.1523/JNEUROSCI.16-19-06246.1996

10.1152/ajpregu.1998.274.3.R783

Schiffrin EL and Touyz RM. Vascular biology of endothelin. J Cardiovasc Pharmacol 32: S2–13, 1998.

Schramek H, Coroneos E, and Dunn MJ. Interactions of the vasoconstrictor peptides, angiotensin II and endothelin-1, with vasodilatory prostaglandins. Semin Nephrol 15: 195–204, 1995.

10.1016/0361-9230(96)00037-8

10.1016/S0014-2999(98)00495-6

10.1038/26233

10.1523/JNEUROSCI.21-08-02669.2001

10.1007/s000110050619

10.1152/ajpregu.1994.266.5.R1670

10.1002/cne.10743

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American Journal of Physiology - Regulatory Integrative and Comparative Physiology

Tập 288 Số 3

R671-R677

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