Effects of Vasopressin Antiserum on the Response of Adrenocorticotropin and Cortisol to Hemorrhage*

To determine if arginine vasopressin (AVP) is involved in the response of ACTH and cortisol (F) to hemorrhage, we examined the effect of injections of AVP-antiserum into the third ventricle in chronically prepared awake cats. Cats were trained to remain unrestrained in a cardboard box. Cats were prepared under halothane and nitrous oxide with aseptic technique. Two to 3 days later, experiments began. Antiserum (5 microliters) to AVP or to oxytocin (OXY) as a control was given 26 min before hemorrhage conducted over 3 min. Thirty minutes after hemorrhage, reinfusion was conducted over 3 min. Each cat received each antiserum in randomized sequence 2-3 days apart. Plasma ACTH and F were measured by RIA. Data were analyzed statistically by analysis of variance. In 12 experiments in 6 cats, ACTH and F increased significantly with 10 ml/kg hemorrhage (P less than 0.01) and to the same extent (P greater than 0.1) after either antiserum. In 20 additional experiments in 10 cats, a submaximal dose of dexamethasone was administered sc 2-3 h before hemorrhage of 15 or 17.5 ml/kg. Under this circumstance, ACTH increased significantly (P less than 0.05) after anti-OXY, but not after anti-AVP (P greater than 0.2) so that during hemorrhage the values of ACTH differed significantly (P less than 0.025). F increased significantly more after anti-OXY than after anti-AVP (P less than 0.025). Changes in arterial pressure, heart rate, and plasma glucose with or without pretreatment with dexamethasone did not differ between groups. Changes in F and ACTH in cats receiving sham injections did not differ from those after anti-OXY. These findings suggest that normally a corticotropin-releasing factor (CRF) or factors act independently of AVP to mediate the response to hemorrhage. However, in the presence of steroid feedback by dexamethasone, the release or action of this CRF(s) is suppressed so that AVP is necessary for a full response. As has been proposed previously by others, AVP could potentiate the action of other CRFs, stimulate their release, or act as a CRF.