Role of neuronal nitric oxide synthase in hypoxia-induced anapyrexia in rats

Anapyrexia (a regulated decrease in body temperature) is a response to hypo xia that occurs in organisms ranging from protozoans to mammals, but very l ittle is known about the mechanisms involved. Recently, it has been shown t hat the NO pathway plays a major role in hypoxia-induced anapyrexia. Howeve r, very little is known about which of the three different nitric oxide syn thase isoforms (neuronal, endothelial, or inducible) is involved. The prese nt study was designed to test the hypothesis that neuronal nitric oxide syn thase (nNOS) plays a role in hypoxia-induced anapyrexia. Body core temperat ure (T-c) of awake, unrestrained rats was measured continuously using biote lemetry. Rats were submitted to hypoxia, 7-nitroindazole (7-NI; a selective nNOS inhibitor) injection, or both treatments together. Control animals re ceived vehicle injections of the same volume. We observed a significant (P < 0.05) reduction in T-c of similar to 2.8 degrees C after hypoxia (7% insp ired O-2), whereas intraperitoneal injection of 7-NI at 25 mg/kg caused no significant-change in T-c. 7-NI at 30 mg/kg elicited a reduction in T-c and was abandoned in further experiments. When the two treatments were combine d (25 mg/kg of 7-NI and 7% inspired O-2), we observed a significant attenua tion of hypoxia-induced anapyrexia. The data indicate that nNOS plays a rol e in hypoxia-induced anapyrexia.