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.