The aim of the present study was to investigate the possibility that endotoxin fever in rats is mediated by arachidonic acid (AA) which in turn is converted to the active metabolites such as prostaglandin (PG) E2, PGF2alpha, thromboxane A2 (TxA2), or prostacyclin (PGI2). Evidence is presented indicating that PGE2 induces fever (not hyperthermia) by acting on the anterior hypothalamic preoptic area. Conversely, both PGF2alpha and AA produce mutually similar hyperthermia and there is no correlation between their microinjection sites in the diencephalon and the observed hyperthermic response. In addition, evidence is presented suggesting that involvement of other metabolites of AA, namely TxA2 and PGI2 in the mediation of endotoxin fever in rats seems unlikely. Only PGE2-induced fever is significantly similar, consistent with the parameters of this study, to endotoxin-induced fever in rats. AA-induced hyperthermia is probably brought about by increased levels of PGF2alpha or both PGF2alpha and PGE2 in the hypothalamus following AA injection. It seems highly unlikely that endotoxin produces fever in rats through the increased availability of free AA or through the activation of the PG endoperoxide synthetase in the hypothalamus. The mechanism by which endotoxin may increase PGF2 levels in the rat hypothalamus remains unknown.
Histamine administered intraventricularly or into the anterior hypothalamic preoptic region induced dose-dependent hypothermia in rats with chronic i.c.v. cannula. This hypothermia was almost totally abolished by both the histamine H1- and H2-receptor antagonists, mepyramine or chloropyramine and metiamide or cimetidine, respectively, give i.c.v. prior to histamine. In behavioural thermoregulation studies histamine considerably diminished the mean duration of dwelling of the rat under the heat lamp. This effect was abolished by histamine H1- but not by H2-receptor antagonists. It is concluded that histamine induces hypothermia by lowering the set point of the hypothalamic thermostat by means of H1-receptors. Histamine H2-receptor blockers antagonized the increase in tail skin temperature after histamine administration, suggesting that h2-receptors are involved in a heat loss mechanism.
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