Post-surgical recovery and time-of-day mask potentiated responses of ACTH to repeated moderate hemorrhage in conscious rats

We determined how changes in the responsiveness of the hypothalamo-pituitar y-adrenal (HPA) system that accompany experimentation affect facilitation o f HPA responses to hemorrhage. Hemorrhage (10 ml/kg over 3 min) was perform ed in conscious, chronically prepared rats. Blood was sampled over 1 h foll owed by reinfusion of shed blood. Hemorrhage was performed either once or t wice separated by 24 h in different groups of animals. To test the effect o f the circadian variation in responsiveness, rats were hemorrhaged on days 4 and 5 after surgery either in the morning (AM) or in the afternoon (PM). The response of ACTH to hemorrhage on day 4 was greater in the PM than in t he AM (P < 0.01). The ACTH response to the second hemorrhage on day 5 was g reater than that to hemorrhage on day 4 only in the AM group (P < 0.01). Th us, facilitation of ACTH responses by prior hemorrhage was evident only in the AM. To determine the effects of surgical recovery, additional experimen ts were done in the AM either early (days 3 and 4) or later (days 6 and 7) after surgery. In these experiments, hemorrhage was performed in all rats o n days 4 and 7 and either hemorrhage or blood sampling alone was performed on day 3 and 6. ACTH did not increase in rats with sampling and no hemorrha ge. ACTH increased more after an initial hemorrhage on day 3 than on day 6 (P < 0.01). ACTH response to hemorrhage on day 4 was greater when preceded by hemorrhage vs sampling on day 3 (P < 0.01). ACTH response to hemorrhage in rats bled twice did not differ on day 3 and day 4. On day 7, the respons e of ACTH in rats that had hemorrhage on day 6 was greater than both their own response on day 6 and the response of a control group with sampling on day 6 (P < 0.01). These results demonstrate potentiation of ACTH responses to hemorrhage by an earlier similar hemorrhage, but clearly indicate that e nhanced sensitivity of the HPA to hemorrhage either by circadian factors or by surgery can mask this effect.