INTERACTION BETWEEN NOREPINEPHRINE AND PROSTAGLANDIN E(2) IN THE PREOPTIC AREA OF GUINEA-PIGS

The release of norepinephrine (NE) and prostaglandin E(2) (PGE(2)) in the preoptic-anterior hypothalamus (POA) by systemically administered pyrogens suggests that both substances may mediate the febrile respons e. To investigate their possible interaction, we measured directly the levels of PGE(2) in the extracellular fluid of the POA of conscious g uinea pigs micro-dialyzed intrapreoptically with exogenous NE over the entire course of their febrile response to endotoxin. Acidified and b uffered NE (NE(a), NE(b)), artificial cerebrospinal fluid (aCSF(a), aC SF(b)), and vehicle (Veh(a), Veh(b)) were tested. All but aCSF(b) depr essed the febrile response to endotoxin. The microdialysis of aCSF(a), aCSF(b), Veh(a), Veh(b), and NE(a) did not change basal preoptic PGE( 2) levels. However NE(b), at a dose that by itself did not affect body temperature (T-b), caused a large elevation in preoptic PGE(2). The i ntravenous injection of endotoxin increased the level of PGE(2) in the POA. NE(b) potentiated this increase, whereas NE(a), aCSF(a), and Veh (b) reduced it; Veh(a) reduced it for the first 60 min and enhanced it for the last 90 min of the experiment. Thus these data suggest that t he low pH of the NE solute and/or its Veh may confound the observed ef fects of NE on the T-b and preoptic PGE(2) induced by endotoxin. We su rmise that this is due to a neurotoxic action of the antioxidants and the acidity of the solution on thermosensitive neurons in the POA. Hen ce, the results of experiments using exogenous, usually acidified, NE preparations that often also contain additives should be interpreted w ith caution.