title: A neurochemical mechanism for hypoxia-induced anapyrexia.
abstract: Hypoxia evokes a regulated decrease in body temperature, a response that has been termed anapyrexia, but the mechanisms involved are poorly understood. Therefore, the present study was undertaken to test the hypothesis that hypoxia-induced anapyrexia results from the activation of cAMP- and cGMP-dependent pathways in the preoptic region (PO). Adult male Wistar rats weighing 230-260 g were used. Body temperature was monitored by biotelemetry, and the levels of cAMP and cGMP were determined in the anteroventral third ventricular region (AV3V), where the PO is located. Using immunohistochemistry, we observed that the PO contains a high density of cAMP- and cGMP-containing cells. Interestingly, hypoxia exposure raised the levels of cAMP and cGMP in the AV3V. Intra-PO microinjection of Rp-cAMPS, an inhibitor of cAMP-dependent protein kinase, attenuated hypoxia-induced anapyrexia. Similarly, intra-PO microinjection of the mixed beta-adrenoceptor/serotonin (5-HT(1A)) receptor antagonist propranolol also impaired the drop in body temperature in response to hypoxia. The reduction in body temperature evoked by intra-PO serotonin, but not epinephrine, was blocked by Rp-cAMPS, indicating the involvement of a preoptic serotonin-cAMP pathway in the development of anapyrexia. Moreover, microinjection of N(G)-monomethyl-l-arginine, an inhibitor of nitric oxide (NO) synthesis, or Rp-cGMPS, an inhibitor of cGMP-dependent protein kinase, into the PO also attenuated hypoxia-induced anapyrexia. In conclusion, the present study supports that hypoxia-induced anapyrexia results from the activation of the serotonin-cAMP and NO-cGMP pathways in the PO.
authors.affiliation: Department of Physiology, Faculty of Medicine of Ribeirao Preto, Department of Morphology, Estomatology and Physiology, Dental School of Ribeirao Preto, University of Sao Paulo, 14040-904 Ribeirao Preto, Sao Paulo, Brazil.
authors.forename: Alexandre A
authors.initials: AA
authors.lastname: Steiner
authors.forename: Maria J A
authors.initials: MJ
authors.lastname: Rocha
authors.forename: Luiz G S
authors.initials: LG
authors.lastname: Branco
mesh_terms: D000818:Animals; D001833:Body Temperature Regulation / Q000187:drug effects; D000242:Cyclic AMP / Q000378:metabolism; D017868:Cyclic AMP-Dependent Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D006152:Cyclic GMP / Q000378:metabolism; D017869:Cyclic GMP-Dependent Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D004837:Epinephrine / Q000494:pharmacology; D000860:Hypoxia / Q000150:complications* / Q000201:enzymology / Q000378:metabolism / Q000503:physiopathology*; D008297:Male; D008845:Microinjections; D009569:Nitric Oxide / Q000378:metabolism; D020030:Nitric Oxide Donors / Q000494:pharmacology; D009599:Nitroprusside / Q000494:pharmacology; D011301:Preoptic Area / Q000378:metabolism; D011433:Propranolol / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D012701:Serotonin / Q000494:pharmacology; D015398:Signal Transduction / Q000187:drug effects; D013997:Time Factors; D014664:Vasodilation
chemical_list: D020030:Nitric Oxide Donors; D009599:Nitroprusside; D009569:Nitric Oxide; D012701:Serotonin; D011433:Propranolol; D000242:Cyclic AMP; D017868:Cyclic AMP-Dependent Protein Kinases; D017869:Cyclic GMP-Dependent Protein Kinases; D006152:Cyclic GMP; D004837:Epinephrine