EVIDENCE FOR ARGININE-VASOPRESSIN AS THE PRIMARY ACTIVATOR OF THE HPAAXIS DURING ADJUVANT-INDUCED ARTHRITIS

1 Adjuvant-induced arthritis (AA) is an experimental inflammation of t he joints that results in chronic activation of the hypothalamo-pituit ary-adrenal (HPA) axis. 2 In this study the role of hypothalamic corti cotrophin-releasing factor (CRF) and arginine vasopressin (AVP) in the regulation of the HPA axis in this condition both in Sprague-Dawley ( SD), and Piebald-Viral-Glaxo (PVG) rats has been further characterized . 3 The increase in AVP peptide content of portal blood (as early as d ay ii), just prior to the onset of arthritis is confirmed and further increases, peaking at day 16 are shown, coincident with the progressio n of inflammation in the PVG rats. 4 The increase in AVP is associated with a significant increase in the expression of AVP but not CRF mRNA s in the medial parvocellular division of the hypothalamic paraventric ular nucleus (PVN) of arthritic SD rats. 5 In the presence of maximal inflammation of SD rats there was a significant decrease in the maximu m binding of [I-125]-Tyr-oCRF to anterior pituitary membranes, whereas AVP receptor concentration in anterior pituitary membranes from both PVG and SD rats showed a significant increase with respect to controls . 6 The basal adrenocorticotrophin (ACTH) secretion in vitro was simil ar in both control and arthritic SD rats but that from arthritic PVG r at pituitaries was significantly greater than the respective controls (436 +/- 91 v 167 +/- 23 pg/tube). The ACTH response of pituitaries of arthritic PVG rats to CRF or the combination of CRF and AVP was signi ficantly higher compared with the controls, although the ACTH response of arthritic SD rat pituitaries was unchanged. 7 The results are cons istent with the view that activation of the parvocellular vasopressin system has an important role in the adaptation of the HPA axis to expe rimentally-induced chronic stress of arthritis.