Av. Gourine, PHARMACOLOGICAL EVIDENCE THAT NITRIC-OXIDE CAN ACT AS AN ENDOGENOUS ANTIPYRETIC FACTOR IN ENDOTOXIN-INDUCED FEVER IN RABBITS, General pharmacology, 26(4), 1995, pp. 835-841
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.