Role of Endogenous Arginine Vasopressin in Potentiating Corticotropin-Releasing Hormone-Stimulated Corticotropin Secretion in Man*

Abstract

Exogenously administered vasopressin (VP) augments ACTH secretion stimulated by CRH. This study was performed to elucidate the role of endogenous VP in potentiating CRH-induced ACTH secretion in man. Synthetic human CRH (100 micrograms) was injected iv into seven normal men after they had been water loaded (20 mL/kg; 60 and 30 min before CRH injection; WL-CRH test) and water deprived (water restriction for 18 h before CRH injection; WD-CRH test). Blood samples were obtained before and 5, 15, 30, 60, 90, and 120 min after CRH injection at 0900 h for determination of plasma ACTH, cortisol, arginine vasopressin (AVP), CRH, and catecholamine levels and osmolality. Urine was obtained immediately before and 120 min after CRH injection for determination of osmolality. The mean plasma AVP levels were significantly higher during the WD-CRH test [1.8 +/- 0.4 (+/- SE) to 1.9 +/- 0.4 pmol/L] than during the WL-CRH test (0.6 +/- 0.1 to 0.9 +/- 0.1 pmol/L). The mean plasma ACTH and cortisol levels rose significantly from basal (4.5 +/- 0.6 pmol/L and 320 +/- 20 nmol/L, respectively) to peak values of 14.0 +/- 2.1 pmol/L at 30 min and 700 +/- 50 nmol/L at 60 min, respectively, during the WD-CRH test. During the WL-CRH test, mean basal plasma ACTH and cortisol levels were 3.5 +/- 0.7 pmol/L and 420 +/- 50 nmol/L, respectively, and reached peak values of 7.7 +/- 1.1 pmol/L at 60 min and 550 +/- 40 nmol/L at 30 min, respectively. Both the mean peak levels and integrated ACTH and cortisol responses were significantly higher during the WD-CRH than during the WL-CRH test. There was no significant difference between the plasma CRH and catecholamine concentrations in both tests. These results suggest that endogenous AVP potentiates CRH-stimulated ACTH secretion and, thus, plays a physiologically significant role in regulating CRH-stimulated ACTH and cortisol secretion in man.

Vasodilatory effect of arginine vasopressin is mediated by nitric oxide in human forearm vessels.

“…Plasma AVP and L-arginine were measured at a commercially available laboratory (SRL, Tokyo, Japan). Plasma AVP was measured in duplicate by RIA kits obtained from Mitsubishi Petrochemical Co. Ltd. (Tokyo, Japan), after Sep-Pak C18 extraction ofplasma as previously described (21,22). The crossreactivity ofantiserum with 8-lysine vasopressin was 0.04%; it was 0.19% with l-deamino-8-D-arginine vasopressin and < 0.01% with oxytosin and 8-arginine vasotocin.…”

Corticotrophin Releasing Factor in Man and Its Measurement: A Review

“…The synergistic interaction of these peptides under less pharmacological conditions has also been demonstrated, since osmotically stimulated endogenous AVP release was found to potentiate hCRF-stimulated corticotrophin secretion in man (Milsom et al, 1985;Watabe et al, 1988;Bahr et al, 1988). However, another study using the ovine peptide merely showed an additive effect of CRF and endogenous AVP (Rittmaster et al, 1986) and patients with diabetes insipidus exhibited normal responses to C R F (Schurmeyer et al, 1984a).…”

Overexpression of vasopressin in the rat transgenic for the metallothionein-vasopressin fusion gene

“…AVP elicits vasoconstriction via V1a receptors located in smooth muscle cells and water reabsorption at the renal collecting duct via V2 receptors (Brownstein 1983). Parvocellular neurons in the PVN project to the median eminence, where AVP is released into pituitary portal vessels in response to stress simultaneously with corticotropinreleasing factor (CRF) (Watabe et al 1988). CRF and AVP are transported to the anterior lobe of the pituitary and promote pro-opiomelanocortin gene activation and adrenocorticotropin secretion.…”