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.