Abstract
We tested the hypothesis that the nitric oxide (NO) pathway in the central nervous system (CNS) plays a role in hypothermia, as well as in the febrile response during experimental septic shock, by regulating vasopressin (AVP) release. Experiments were performed on male Wistar rats treated with N G-nitro-l-arginine methyl ester (l-NAME), a non-selective NO synthase (NOS) inhibitor, injected intracerebroventricularly (250 µg/1 μl) 30 min before lipopolysaccharide (LPS) 1.5 mg/kg i.v. injection. One hour after LPS administration we observed a significant drop in body temperature (hypothermic response), followed by a temperature increase after the second hour (febrile response), which remained until the end of the experiment. Increased plasmatic AVP levels were concomitantly observed during hypothermia, nearly returning to basal levels during the febrile phase. When l-NAME was administered with LPS, plasmatic AVP concentrations remained high throughout the experiment, hypothermia was accentuated and the febrile response was abolished. Additionally, pre-treatment with β-mercapto-β,β-cyclopentamethylenepropionyl1, O-Et-Tyr2, Val4, Arg8-vasopressin, an AVP V1 receptor blocker (10 µg/kg) administered i.v., reduced hypothermia and exacerbated the febrile response to endotoxin. In conclusion, our data indicate that the central NO pathway plays an inhibitory role in AVP release during experimental septic shock, which seems to be critical for the thermoregulation during this pathophysiological state.
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Acknowledgements
We would like to thank Leila M.M. Alves and Flávia F. Salata for the excellent technical assistance. This study was supported by Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP), Fundação de Amparo ao Ensino e à Pesquisa do Hospital das Clínicas da Faculdade de Medicina de Ribeirão Preto (FAEPA), Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq), and PRONEX.
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Giusti-Paiva, A., Branco, L.G.S., de Castro, M. et al. Role of nitric oxide in thermoregulation during septic shock: involvement of vasopressin. Pflugers Arch - Eur J Physiol 447, 175–180 (2003). https://doi.org/10.1007/s00424-003-1164-2
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DOI: https://doi.org/10.1007/s00424-003-1164-2