PHARMACOLOGICAL EVIDENCE THAT NITRIC-OXIDE CAN ACT AS AN ENDOGENOUS ANTIPYRETIC FACTOR IN ENDOTOXIN-INDUCED FEVER IN RABBITS

1. This study investigates the effects of the nitric oxide donors on l ipopolysaccharide-induced fever in rabbits, and the effect of brain ni tric oxide synthase inhibition on the febrile response in pyrogen tole rant animals. 2. The febrile response was reduced by intravenous injec tions of the nitric oxide donors molsidomine (1.0 mg/kg) and isosorbid e dinitrate (0.5 mg/kg) 60 min after intravenous treatment with lipopo lysaccharide. 3. The magnitude of fever was also attenuated by intrace rebroventricular administration of molsidomine (75 mu g). 4. Intracere broventricular pretreatment with the nitric oxide synthase inhibitor, N-G-nitro-L-arginine (100 mu g) 10 min before the injection of lipopol ysaccharide significantly enhanced the febrile response in pyrogen tol erant animals. 5. The results suggest that nitric oxide is involved in the central mechanisms of thermoregulation during fever as one of the effective endogenous antipyretics.