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

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.