A norepinephrine-cyclic AMP link in the hypothalamic pathways which mediate fever induced by endotoxin and prostaglandin E2 in the rat.

The changes in rectal temperature, metabolic rate, cutaneous temperatures and respiratory evaporative heat loss produced by an injection of a bacterial endotoxin piromen (4-40 ng in 1 microliter) into the anterior hypothalamus were assessed in conscious rats in both sexes from a wide range of body mass and at various ambient temperatures (TaS). Intrahypothalamic injection of piromen increased metabolism and decreased cutaneous temperatures which led to fever in rats at Ta 8-30 degrees C. The monophasic fever was not significantly correlated with either body mass, sex difference of the Ta at which the experiments are carried out. Furthermore, daily intrahypothalamic injections of piromen produced no pyrogenic tolerance. Intrahypothalamic injections of either prostaglandin E2, norepinephrine, aminophylline or dibutyryl cyclic AMP also produced increased metabolism and decreased cutaneous temperature which led to fever at Ta 8-30 degrees C. In addition, the fever induced by intrahypothalamic injections of piromen, prostaglandin E2 or nor-epinephrine was greatly antagonized by pretreatment with intrahypothalamic injections of alpha or beta adrenergic antagonist. However, the fever induced by dibutyryl cyclic AMP or aminophylline was not affected by pretreatment with adrenergic receptor blockade. The data indicate that a norepinephrine- cyclic AMP link occurs in the hypothalamic pathways which mediate the piromen-induced or the prostaglandin E2-induced fever in rats.