Central blockade of nitric oxide synthesis induces hyperthermia that is prevented by indomethacin in rats

Michael L. Mathai, Imogen Arnold, Mark A. Febbraio, Michael J. McKinley

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The effect of blocking brain nitric oxide (NO) synthesis on body temperature regulation was tested in conscious rats. NO synthase was inhibited by administration of equivalent doses of N G-nitro-l-arginine methyl ester (l-NAME) or N G-monomethyl l-arginine monoacetate (l-NMMA) into a lateral cerebral ventricle (ICV) and core temperature was monitored. An ICV injection of 300 μg l-NAME increased colonic temperature in rats (n=8) by 1.9±0.1°C (P<0.001). The increase in temperature in response to blockade of NO synthesis was significant by 1 h after injection and sustained for more than 3 h. The hyperthermic response to central NO blockade (using l-NMMA) was found to be dose-dependent between 2.8 to 282 μg. Intravenous administration of l-NAME at the highest dose used in the study (300 μg) had no effect on temperature, indicating that the mechanism was mediated by the brain. Pre-treatment with indomethacin (300 μg) blocked hyperthermic responses to ICV l-NAME (300 μg) administration. We conclude that, blockade of nitric oxide induces a cyclooxygenase-dependent hyperthermia in conscious rats that is mediated by the brain.

Original languageEnglish
Pages (from-to)401-405
Number of pages5
JournalJournal of Thermal Biology
Publication statusPublished - 1 Oct 2004
Externally publishedYes


  • Brain
  • Hyperthermia
  • l-NAME
  • Prostaglandin synthesis
  • Thermoregulation

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