ABSENCE OF GLUCOCORTICOID NEGATIVE FEEDBACK TO MODERATE HEMORRHAGE INCONSCIOUS RATS

Hypothalamic-pituitary-adrenal (HPA) axis responses to stressors elici t and are modulated by glucocorticoids. In the present study, pituitar y-adrenal responses to repeated 14 ml/kg (almost-equal-to 20%) blood l osses separated by 90 min were evaluated in chronically cannulated mal e rats. Plasma adrenocorticotropin (ACTH) and corticosterone (Cort) le vels peaked by 9 and 18 min after hemorrhage, respectively. ACTH retur ned toward prestimulus values upon retransfusion, whereas Cort remaine d elevated. Repeated hemorrhage was associated with significantly larg er pituitary-adrenal secretory responses, as compared with the initial hemorrhage. These responses were characterized by a more rapid rate o f rise in plasma ACTH and delayed Cort secretion. Treatment of rats wi th intravenous Cort in place of the initial hemorrhage was without eff ect on the magnitude of pituitary-adrenal responses to a hemorrhage 90 min later. From these observations, it is suggested that 1) the physi cal stressor of hemorrhage elicits reproducible activation of the HPA axis in rats, 2) HPA axis activation after hemorrhage appears to be me diated via glucocorticoid-independent pathways, and 3) responsiveness to repeated hemorrhage is modestly amplified by some aspect of the ini tial stimulus.