SUBDIAPHRAGMATIC VAGOTOMY SUPPRESSES ENDOTOXIN-INDUCED ACTIVATION OF HYPOTHALAMIC CORTICOTROPIN-RELEASING HORMONE NEURONS AND ACTH-SECRETION

In order to assess the possibility that endotoxin-induced activation o f the hypothalamus-pituitary-adrenal (HPA) axis is mediated by vagal a fferents, we studied the effects of transection of the vagal nerves on endotoxin-induced Fos expression in hypothalamic corticotropin-releas ing hormone (CRH) neurons and plasma ACTH and corticosterone responses . Groups of rats were subjected to sham surgery, complete subdiaphragm atic vagotomy (SVGX), or selective transection of the hepatic branch ( HVGX). Two weeks after surgery, endotoxin or saline was injected i.p. and rats were sacrificed by decapitation two hours later. SVGX blocked or attenuated the ACTH response to 20 and 250 mu g/kg endotoxin, resp ectively. HVGX did not suppress the ACTH response to either endotoxin dose. In addition, corticosterone responses were not affected by SVGX or HVGX. The endotoxin-induced Fos expression in CRH neurons was suppr essed in SVGX, but not in HVGX animals. These observations lead us to postulate that the CRH and ACTH responses to a low dose of endotoxin a re mediated by vagal afferents. The responses to a high dose of endoto xin involve additional neuronal or humoral pathways.