Effects of nitric oxide synthase inhibitors on the febrile response to muramyl dipeptide and lipopolysaccharide in rats

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dc.contributor.authorKamerman, P.R.
dc.contributor.authorMitchell, D.
dc.contributor.authorLaburn, H.P.
dc.contributor.departmentSchool of Physiology, University of the Witwatersrand, Medical School, 7 York Road, Parktown, 2193, South Africa. Kamermanpr@physiology.wits.ac.zaen_US
dc.date.accessioned2020-06-26T13:09:56Z
dc.date.available2020-06-26T13:09:56Z
dc.date.epub2002-06-14
dc.date.issued2002
dc.description.abstractWe have administered aminoguanidine, a relatively specific inhibitor of inducible nitric oxide synthase, and N-nitro-L-arginine methyl ester (L-NAME), an unspecific nitric oxide synthase inhibitor, to rats made febrile with the gram-positive pyrogen, muramyl dipeptide and gram-negative pyrogen, lipopolysaccharide. Sprague-Dawley rats, housed individually at approximately 25 degrees C with a 12:12 h light:dark cycle (lights on 0700 hours), were injected (at 0900 hours) intraperitoneally with 50 mg/kg aminoguanidine, 25 mg/kg or 50 mg/kg L-NAME, and intramuscularly with 500 microg/kg muramyl dipeptide or 100 microg/kg lipopolysaccharide. Pyrogen injections were spaced at least 14 days apart. Body temperature was measured throughout the study in unrestrained animals using radio-telemetry. Neither muramyl dipeptide nor lipopolysaccharide-induced fevers were affected by aminoguanidine. However, L-NAME administration inhibited muramyl dipeptide and lipopolysaccharide-induced fevers, but only for the 1st 2-4 h of the fevers (two-way ANOVA, P<0.05). After the initial inhibition, lipopolysaccharide fevers developed normally. Therefore, constitutively expressed nitric oxide synthase appears to be involved in the initial phases of fever genesis of gram-negative and gram-positive fevers in rats. On the other hand, inducible nitric oxide synthase appears not to play a role in these fevers.en_US
dc.description.sponsorshipWe are grateful to Deryn Petty for surgery, Lennox Nqobo and the staff of the Central Animal Service for their assistance with the experiments, and Andrea Fuller for comments on the manuscript. This work was funded by grants from the Medical Research Council of South Africa, and the Medical Faculty Research Endowment Fund and University Research Council of the University of the Witwatersranden_US
dc.identifier.citationKamerman PR, Mitchell D, Laburn HP. Effects of nitric oxide synthase inhibitors on the febrile response to muramyl dipeptide and lipopolysaccharide in rats. JOURNAL OF COMPARATIVE PHYSIOLOGY Ben_US
dc.identifier.issn0174-1578.
dc.identifier.journalJournal of comparative physilogyen_US
dc.identifier.urihttps://infospace.mrc.ac.za/handle/11288/595251
dc.language.isoenen_US
dc.publisherSpringeren_US
dc.relation.urlhttp://explore.bl.uk/primo_library/libweb/action/display.do?en_US
dc.relation.urltabs=detailsTab&gathStatTab=true&ct=display&fn=search&doc=ETOCRN116998300&indx=1&recIds=ETOCRN116998300.en_US
dc.research.unitClosed Unitsen_US
dc.rightsAttribution 3.0 United States*
dc.rights.urihttp://creativecommons.org/licenses/by/3.0/us/*
dc.titleEffects of nitric oxide synthase inhibitors on the febrile response to muramyl dipeptide and lipopolysaccharide in ratsen_US
dc.typeArticleen_US
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