Role of nitric oxide in hypoxia inhibition of fever

Hypoxia causes a regulated decrease in body temperature (T-b), and nitric o xide (NO) is now known to participate in hypoxia-induced hypothermia. Hypox ia also inhibits Lipopolysaccharide (LPS)-induced fever. We tested the hypo thesis that NO may participate in the hypoxia inhibition of fever. The rect al temperature of awake, unrestrained rats was measured before and after in jection of LPS, with or without concomitant exposure to hypoxia, in an expe rimental group treated with N-omega-nitro-L-arginine (L-NNA) for 4 consecut ive days before the experiment and in a saline-treated group (control). L-N NA is a nonspecific NO synthase inhibitor that blocks NO production. LPS ca used a dose-dependent typical biphasic rise in T-b that was completely prev ented by hypoxia (7% inspired oxygen). L-NNA caused a significant drop in T -b during days 2-4 of treatment. When LPS was injected into L-NNA-treated r ats, inhibition of fever was observed. Moreover, the effect of hypoxia duri ng fever was significantly reduced. The data indicate that the NO pathway p lays a role in hypoxia inhibition of fever.