Involvement of central vs. peripheral mechanisms in mediating sympathoadrenal activation in endotoxic rats

Abstract

The contribution of central vs. peripheral mechanisms in mediating increases in plasma norepinephrine (NE) and epinephrine (Epi) during endotoxicosis were studied. Plasma catecholamine responses after endotoxin were assessed in conscious animals and in animals without central regulatory mechanisms (pithed rats). In conscious rats, endotoxin (1.5 mg/kg i.v.) induced a marked elevation in plasma NE after 90 min (3-fold), but elevations were not seen in pithed rats. Endotoxin also induced a profound increase (12- to 13-fold) in plasma Epi in conscious rats, but increases were less (2- to 3-fold) and delayed in pithed rats. These results suggest that central mechanisms are essential in plasma NE response to endotoxic challenge, whereas plasma Epi response involves both central and peripheral mechanisms, with the former being dominant. In conscious adrenal-denervated animals, plasma Epi was not elevated until 90 min postendotoxin. This delayed Epi elevation was approximately one-third of the maximal response observed in conscious adrenal-intact rats. In pithed adrenal-denervated rats, plasma Epi at 90 min postendotoxin was also increased to a level comparable to that in pithed adrenal-intact rats. These results imply that a significant fraction of peripheral release of Epi with endotoxicosis is nonneurogenic.