Combined hypervolemia and hypoosmolality alter hypothalamic-pituitary-adrenal axis response to endotoxin stimulation

Changes in corticotropin (ACTH) and glucocorticoid secretion have been desc ribed during disturbances of body fluid homeostasis and attributed to alter ations in arginine vasopressin (AVP) secretion from magnocellular hypothala mic neurons. In order to further characterize the mechanisms involved in th e interactions between body fluid alterations and pituitary adrenal functio n, we manipulated osmolality and volemia in sheep under stimulation of the pituitary-adrenal axis by acute injection of endotoxin. We have recently sh own that endotoxin injection induces a long-lasting release of both cortico tropin releasing hormone (CRH) and AVP into hypophysial portal blood, and a n early stimulation of AVP secretion into peripheral vessels, thus suggesti ng a joint activation of magnocellular and parvocellular neurons of the PVN . We used the same experimental model to investigate the effect of combined volume loading and plasma dilution (achieved by 1-deamino-8-D-arginine (dD AVP) administration together with infusion of 2 liters of 2.5% glucose solu tion) on CRH, AVP, ACTH and cortisol responses to endotoxin stimulation. In volume-loaded animals, ACTH and cortisol responses to endotoxin were signi ficantly blunted and we observed a parallel decrease in portal CRH and jugu lar and portal AVP levels. These data show that hypoosmolality and/or hyper volemia reduce(s) ACTH and cortisol response to stress in sheep as in other species. They strongly suggest that this reduction in ACTH and cortisol re sponses to endotoxin involve not only magnocellular hypothalamic neurons se creting AVP, as usually assumed, but also PVN parvocellular neurons secreti ng both CRH and AVP.