Participação do óxido nítrico da substância cinzenta periaqueductal dorsolateral na febre induzida por estresse de contenção física em ratos
Abstract
Nitric oxide (NO) is a gaseous neurotransmitter that has an important role for cyclic GMPdependent
pathway in brain regions involved in thermoregulation in different conditions as
fever-induced inflammatory agents. It is known that NO also acts in the brain to mediate
fever front response to stress physical restraint, but still are not known your action site. In
this context, the dorsolateral periaqueductal gray (PAGdl) is a potential site of action of
NO, it is involved in stress responses, defensive behaviors and thermoregulation, and
express large amounts of the enzyme NO synthase, which is responsible for the synthesis
NO. Given these considerations, the hypothesis of this study was that NO exerts a role in
the PAGdl cGMP-dependent modulation of the febrile response to stress of physical
restraint in rats. To test this hypothesis, we investigated the effect of microinjections of the
non-selective NOS inhibitor, L-NMMA, and guanylate cyclase soluble selective inhibitor,
ODQ, on PAGdl on body temperature (Tc) and heat loss index ( IPC; expresses the
activation of heat conservation mechanism during fever) submitted or not to the stress of
physical restraint. There was also the effect of L-NMMA intra PAGdl on oxygen
consumption (thermogenesis index) of rats subjected to stress from physical restraint. In
conditions of eutermia (no stress), none of the treatments affected the Tc and the IPC of the
mice. The Tc increased and the IPC reduced during physical restraint, with a large increase
in the IPC shortly after the end of the contention, coinciding with the return of Tc to the
initial values. The inhibition of NO synthesis in PAG during physical containment caused a
greater increase in Tc when compared to the vehicle without affecting the IPC. Similar
effect on Tc and the IPC was caused by ODQ. Oxygen consumption increased during
physical restraint, which were higher in animals treated with L-NMMA. The results
indicate that NO in PAGdl has an antipyretic effect on physical restraint induced fever in
rats by inhibiting the thermogenic effector, but without affecting the conservation of heat.
This effect seems to be dependent of the NO-cGMP pathway.