RESUMO
It has been shown that the NO pathway plays a major role in restraint stress-induced fever, and that the neuronal nitric oxide synthase (nNOS) seems to be the NOS isoform that accounts for the pyretic effect of NO in psychological stress-induced fever. However, no information exists as to localization of the nNOS, i.e., in the peripheral or in the central nervous system (CNS). Thus, in the present study, we tested the hypothesis that NO arising from nNOS in the CNS participates in restraint stress-induced fever. Moreover, we also assessed the involvement of cyclic guanosine monophosphate (cGMP) in the mediation of the NO effects. To this end, intracerebroventricular S-methyl-L-thiocitrulline (SMTC; a selective nNOS inhibitor), sodium nitroprusside (an NO donor) or Rp-guanosine 3',5'-cyclic monophosphothioate triethylamine (Rp-cGMPS; a specific membrane-permeable inhibitor of the activation by cGMP of cGMP-dependent protein kinase) were injected, and the colonic temperature (T(c)) of restrained or unrestrained rats was recorded. Both SMTC (0.5 mg/mul) and Rp-cGMPS (10 mug/mul) intracerebroventricular injections enhanced restraint fever, whereas intracerebroventricular injections of sodium nitroprusside (100 mug/mul) reduced this response. These data indicate that NO produced in the CNS, arising from nNOS and acting via cGMP, plays an antipyretic role in the restraint stress-induced fever.
Assuntos
Regulação da Temperatura Corporal/fisiologia , GMP Cíclico/metabolismo , Imobilização/efeitos adversos , Neurônios/metabolismo , Óxido Nítrico Sintase/metabolismo , Estresse Fisiológico/fisiopatologia , Adaptação Fisiológica , Animais , Febre/etiologia , Febre/fisiopatologia , Masculino , Óxido Nítrico/metabolismo , Ratos , Ratos Wistar , Transdução de Sinais/fisiologia , Estresse Fisiológico/complicaçõesRESUMO
Nitric oxide (NO) has been shown to be an important modulator of the febrile response to pyrogens and to psychological stress. In the present study, we aimed to identify the nitric oxide synthase (NOS) isoform (neuronal or inducible, nNOS and iNOS, respectively) involved in restraint stress fever. Colonic temperature (Tc) was measured in unanesthetized rats before and after treatment with the more selective nNOS inhibitor 7-nitroindazole or with the selective iNOS inhibitor aminoguanidine (AG) under unrestrained or restrained conditions. Intraperitoneal injection of AG (25 or 50 mg/kg) did not affect restraint fever, indicating that iNOS is unlikely to be involved in restraint fever. On the other hand, intraperitoneal injection of 7-nitroindazole (25 mg/kg) significantly attenuated the rise in the Tc caused by restraint stress, whereas it caused no change in Tc of euthermic animals. These data show that NO produced by nNOS plays an important role in the genesis of restraint stress-induced fever.