Thermoregulatory effects of cyanide and azide in the toad, Bufo marinus

An important adaptation to hypoxia is a regulated reduction in body temperature (T-b; anapyrexia), presumably because it lowers metabolic rate when oxygen supply is limited. Although this beneficial response occurs in organisms ranging from protozoans to mammals, little is known of the cellular mechanisms involved. We showed previously that inhibition of oxidative phosphorylation mediates hypoxia-induced anapyrexia in the paramecium. In this study, we tested the hypothesis that inhibition of oxidative phosphorylation also causes anapyrexia in a vertebrate, Bufo marinus. T-b in toads was measured in a thermal gradient 24 h before and 24 h after administration of either NaCN or NaN3, both inhibitors of oxidative phosphorylation. Subcutaneous NaCN (0.6 mmol/kg) reduced T-b from 29.1 +/- 0.8 to 19.6 +/- 0.6 degrees C (P = 0.002). Infusion of NaCN (0.6 mu mol/kg) into the fourth ventricle of the brain reduced T-b from 30.0 +/- 0.9 to 24.8 +/- 1.2 degrees C (P = 0.01). Responses to NaN3 were similar to the NaCN responses. Control injections and subcutaneous injections of 0.6 mu mol/kg NaCN and NaN3 had no significant effect on T-b (P > 0.32). Neither NaCN nor NaN3 had significant effects on arterial PO2, PCO2, or pH at 26 degrees C. These results indicate that inhibition of oxidative phosphorylation in the central nervous system leads to the selection of cooler temperatures. Thus reduced oxidative phosphorylation within the brain may be an important factor eliciting hypoxia-induced anapyrexia.