O. Shido et al., ROLE OF INTRAPREOPTIC NOREPINEPHRINE IN ENDOTOXIN-INDUCED FEVER IN GUINEA-PIGS, The American journal of physiology, 265(6), 1993, pp. 180001369-180001375
The peripheral administration of pyrogens has been shown previously to
affect the activity of central noradrenergic neurons, but the effects
have been variable and no consensus has emerged regarding their funct
ional significance. Because norepinephrine (NE) microdialyzed into the
preoptic area (PO) of the anterior hypothalamus of conscious guinea p
igs is hypothermizing, the possibility was investigated whether NE mig
ht be a febrilytic rather than a febrigenic mediator. Intravenous inje
ctions of Salmonella enteritidis lipopolysaccharide (2.0 mug/kg) evoke
d a bimodal fever, which was attenuated in a dose-dependent manner by
NE microdialyzed (10 or 20 mug/mul at a rate of 2 mul/min for various
durations) into the PO. The alpha2-adrenergic receptor antagonists rau
wolscine (1 or 2 mug/mul) and yohimbine (1 mug/mul) microdialyzed intr
apreoptically significantly reduced the trough of body (core) temperat
ure (T(c)) between the first and second peaks of the bimodal fever and
prolonged the overall febrile course. None of these effects was assoc
iated with changes in skin temperature. The level of NE (assayed by hi
gh-performance liquid chromatography with electrochemical detection) i
n the preoptic extracellular fluid collected by intracerebral microdia
lysis was significantly elevated at the end of each rising phase of th
e bimodal fever, just before or about the tune when T(c) began to fall
, compared with pyropyrogen-free saline controls at the same times. Th
ese results suggest that intrapreoptic NE may have a thermolytic effec
t on fever by reducing metabolic heat production and may thus play a p
hysiological role in the initiation of febrilysis in guinea pip.