Absence of glucocorticoid negative feedback to moderate hemorrhage in conscious rats

Hypothalamic-pituitary-adrenal (HPA) axis responses to stressors elicit and are modulated by glucocorticoids. In the present study, pituitary-adrenal responses to repeated 14 ml/kg (approximately 20%) blood losses separated by 90 min were evaluated in chronically cannulated male rats. Plasma adrenocorticotropin (ACTH) and corticosterone (Cort) levels peaked by 9 and 18 min after hemorrhage, respectively. ACTH returned toward prestimulus values upon retransfusion, whereas Cort remained elevated. Repeated hemorrhage was associated with significantly larger pituitary-adrenal secretory responses, as compared with the initial hemorrhage. These responses were characterized by a more rapid rate of rise in plasma ACTH and delayed Cort secretion. Treatment of rats with intravenous Cort in place of the initial hemorrhage was without effect on the magnitude of pituitary-adrenal responses to a hemorrhage 90 min later. From these observations, it is suggested that 1) the physical stressor of hemorrhage elicits reproducible activation of the HPA axis in rats, 2) HPA axis activation after hemorrhage appears to be mediated via glucocorticoid-independent pathways, and 3) responsiveness to repeated hemorrhage is modestly amplified by some aspect of the initial stimulus.