Pituitary-adrenal responses to repeated small hemorrhage in conscious dogs

Potentiated pituitary-adrenocortical responses to the second of two identical small hemorrhages, spaced 24 h apart, are seen in the pentobarbital sodium-anesthetized dog. To investigate the role of pentobarbital anesthesia in these results and to better define the range of the effect, we studied awake trained dogs with chronic adrenal venous catheters. Each dog was bled an amount between 8.7 and 21.8% of measured blood volume [¹³¹I](MBV) over 3 min, and peripheral and adrenal blood were sampled. Blood was reinfused 1 h later, and the dogs were fed. The same hemorrhage and experimental protocol were repeated 24 h later. Steroids were assayed by high-performance liquid chromatography-ultraviolet (HPLC-UV) and adrenocorticotropic hormone (ACTH) by radioimmunoassay (RIA). Secretory rates of cortisol were calculated using measured adrenal blood flow rates. Maximal secretion of cortisol was determined after injection of 100 mU ACTH following each experiment. Dogs whose day 1 cortisol secretion after hemorrhage was submaximal (hem volume = 14.8 ± 3.7% MBV; n = 7) showed a greater cortisol secretory response to the same hemorrhage on day 2 (P < 0.005). This increased cortisol response on day 2 was accompanied by an increased ACTH presentation rate (APR) (P < 0.025) and by increased adrenal sensitivity to ACTH (P < 0.025). The increased APR was caused by both an increased venous ACTH and by an increased adrenal blood flow. If posthemorrhage cortisol secretion was maximal on day 1, ACTH, APR, and ABF were not different on the 2 days. No hemodynamic differences were seen to explain these findings. These results confirm and extend our previous results. We conclude 1) the observed potentiation is independent of the central cardiovascular and behavioral effects of pentobarbital; 2) the potentiation after small hemorrhage does not increase the maximal cortisol secretory rate and therefore may only be seen after submaximal stimuli; 3) the effect appears to involve both an increase in ACTH and an increase in adrenal sensitivity to ACTH; 4) adrenal blood flow and intra-adrenal flow distribution may play an important role in this effect.