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.