Effects of Incremental Infusions of Arginine Vasopressin on Adrenocorticotropin and Cortisol Secretion in Man*

Abstract

Arginine vasopressin (AVP) regulates ACTH release under certain conditions, and exogenously administered AVP is used clinically to stimulate ACTH secretion. We attempted to determine at what plasma concentration AVP can stimulate ACTH release. Six normal men were given infusions of AVP (Ferring) or vehicle between 1600 and 1700 h on five occasions: 1) saline (30 mL/h); 2) 10 ng AVP/min; 3) 30 ng AVP/min; 4) 100 ng AVP/min; and 5) 300 ng AVP/min. Plasma AVP, ACTH, and cortisol concentrations were measured every 10 min during the infusions. Basal plasma AVP levels were less than 1 ng/L (less than 0.92 pmol/L). The lowest AVP dose raised plasma AVP into the range found in fluid-deprived subjects (7-8 ng/L;6.5-7.3 pmol/L), but had no effect on plasma ACTH concentrations. AVP in a dose of 30 ng/min also had no effect. The 100 ng AVP/min dose raised plasma AVP concentrations to 51.4-65.5 ng/L (46-60 pmol/L). This increase led to a transient insignificant increase in plasma ACTH from 13.9 +/- 1.2 (+/- SEM) ng/L (3.1 +/- 0.3 pmol/L) to 20.0 +/- 1.4 ng/L (4.4 +/- 0.3 pmol/L), while plasma cortisol rose significantly from 146 +/- 10 to 209 +/- 19 nmol/L (P less than 0.01) after 60 min of infusion. The 300 ng AVP/min dose raised plasma AVP levels to about 260 ng/L (239 pmol/L); the maximal plasma ACTH and cortisol levels were 39.5 +/- 5.0 ng/L (8.7 +/- 1.1 pmol/L; P less than 0.01) and 348 nmol/L (P less than 0.01), respectively. Thus, peripheral plasma AVP levels have to be raised high above the physiological range before ACTH release is stimulated. We conclude that any AVP reaching the adenohypophysis through the peripheral circulation is of much less importance for the regulation of ACTH secretion than is AVP derived from the pituitary portal circulation.

A Synergistic Adrenocorticotropin Response to Naloxone and Vasopressin in Normal Humans: Evidence That Naloxone Stimulates Endogenous Corticotropin-Releasing Hormone

“…However, no published studies of CRH/AVP synergy em ploying exogenous AVP have measured plasma AVP con centrations. Dose-response studies of intravenous AVP administration to normal humans have demonstrated that while a peripheral plasma AVP concentration of 60 pmol/1 does not stimulate ACTH and cortisol release [42], levels of 135 pmol/1 cause a significant rise in both ACTH and cortisol [43]. Considerably lower AVP concentrations of 5-10 pmol/1, achieved by hypertonic saline infusion, will augment the stimulatory effect of synthetic CRH in vivo [6,7], and this is consistent with reports that very low intra venous doses of AVP or LVP, which do not by themselves significantly increase ACTH levels above basal, still sub stantially increase the ACTH response to human or ovine 203 CRH [41,[44][45][46].…”

Vasopressin V1a and V1b Receptors: From Molecules to Physiological Systems

“…In addition, AVP is known to directly stimulate glucocorticoid secretion via the V1a receptor in the human adrenal cortex (196,401). In humans, Hensen et al (213) showed that AVP administration, which led to an insignificant increase in the plasma ACTH level, significantly increased the plasma cortisol level. Moreover, peripheral administration of AVP was found to cause ACTH secretion, which resulted in glucocorticoid secretion from the adrenal cortex, when the plasma AVP level was above the physiological range (213).…”

“…In humans, Hensen et al (213) showed that AVP administration, which led to an insignificant increase in the plasma ACTH level, significantly increased the plasma cortisol level. Moreover, peripheral administration of AVP was found to cause ACTH secretion, which resulted in glucocorticoid secretion from the adrenal cortex, when the plasma AVP level was above the physiological range (213). Thus AVP can stimulate glucocorticoid secretion directly through the adrenal V1a receptor and indirectly through ACTH secretion (24,166,176).…”

Dose Response of Arginine Vasopressin to the CCK-B Agonist Pentagastrin

“…The median eminence/portal pool of AVP is directly linked to ACTH release (Hensen et al 1988), and if this were the source of AVP in our subjects we would expect a much tighter link to ACTH levels. Posterior pituitary AVP is released into the peripheral circulation and comprises a separate pool, which probably does not directly influence ACTH release.…”

“…Posterior pituitary AVP is released into the peripheral circulation and comprises a separate pool, which probably does not directly influence ACTH release. Much higher levels of peripherally measured AVP are usually needed before an AVP-mediated ACTH response is elicited (Hensen et al 1988). If the posterior pituitary was the source of the AVP response to pentagastrin in our subjects, then the weak relationship with ACTH release that we did detect could be explained by the presence of CCK-B receptors, with similar sensitivities, in both the anterior and posterior pituitary.…”