Effects of a V1-vasopressin antagonist on ACTH release following vasopressin infusion or insulin-induced hypoglycemia in normal men

Abstract

Experimental evidence indicates that arginine vasopressin contributes to the release of adrenocorticotropic hormone under certain conditions. We studied for the first time the AVP antagonist [d(CH2)5 Tyr(Me)AVP] in 6 normal men in order to evaluate the possible role of AVP as an ACTH-releasing hormone during insulin-induced hypoglycemia. To test the agent's capacity to inhibit an ACTH release by exogenous AVP, we compared the ACTH response to an infusion of 300 ng AVP/min a. 30 min after injection of 5 \g=m\g/kg of the antagonist, b. after injection of placebo (0.9% NaCl). Plasma ACTH levels during AVP infusion rose from 17.2\m=+-\1.6ng/l (3.8\m=+-\0.35 pmol/l) to 31.7\m=+-\4.2ng/l (7.0\m=+-\0.92pmol/l) at 40 min after injection of the antagonist, the difference to the control-group (increment from 16.5\m=+-\1.2 ng/l (3.6\m=+-\0.26pmol/l) to 41.8\m=+-\3.5 ng/l) (9.2\m=+-\0.77pmol/l) being significant (p<0.05). Peak plasma cortisol levels were 323\m=+-\42and 529\m=+-\52nmol/l, respectively (p<0.05). We then tested the compound in the same subjects during an insulin-induced hypoglycemia; 30 min after administration of 10 \g=m\g/kg of the AVP antagonist or placebo, all subjects received 0.12 IU/kg of normal insulin, thus inducing a fall of blood glucose levels below 2 mmol/l. The AVP antagonist caused a moderate but insignificant reduction of the rise in plasma ACTH and a slightly greater, significant reduction of the increment in plasma cortisol (350\m=+-\19 nmol/l with antagonist and 469\m=+-\90nmol/l with placebo, p<0.05) during insulininduced hypoglycemia. The results indicate that a. the AVP antagonist partly inhibits the stimulatory effect of infused AVP on ACTH release in normal men; b. a slightly higher dose of this competitive AVP antagonist inhibits ACTH and cortisol stimulation by hypoglycemia only very little. The importance of AVP as an ACTH\x=req-\ releasing factor in the latter condition may have been underestimated by our experiment, since AVP concentrations in hypophyseal portal blood during hypoglycemia probably were higher than during the AVP infusion experiment.It has been recognized for many years that acute hypoglycemia is a potent stimulus for the release of several anterior pituitary hormones. Hypoglycemia also stimulates the release of arginine vasopressin in humans (1) and rats (2). The physiological re¬ levance of the AVP response to hypoglycemia is unclear. A variety of studies have demonstrated an AVP-induced release of adrenocorticotropic hor¬ mone and a potentiation of the ACTH response to corticotropin-releasing hormone by AVP (3-8), sug¬ gesting that this peptide is involved in ACTH se¬ cretion under certain conditions. Most of the above-mentioned studies attempted to define the role of vasopressin as an ACTH secretagogue by giving it exogenously. Recently, se¬ veral competitive antagonists were synthesized and tested in animals and humans (9-11). The present study was carried out to investigate the role of en¬ dogenous vasopressin in inducing ACTH release during insulin-induced hypo...

The role of vasopressin in the nicotine-induced stimulation of ACTH and cortisol in men

“…The AVP antagonist, in a dosage of 5 gg/kg body weight, had no intrinsic effect on the hormones measured. Although the antagonist, given in the same dosage, has been proved to attenuate the ACTH response to intravenous AVP by about 50% [11], it only slightly attenuated the response of ACTH and cortisol to nicotine infusion.…”

Is there an undiscovered neurocircuit for regulating GH secretion? -Pitfalls of GHRP-2 and ITT as GH provocative tests-

“…GH and ACTH, and AVP are secreted from the anterior and posterior pituitaries, respectively and hypothalamic hormones may regulate their secretion [1,2,6,7]. The proposed mechanism by which ITT stimulates GH and ACTH, and AVP release is due to stimulation of GHRH and CRH and inhibition of SRIF release from the hypothalamus [2,6,7] and GHRP-2 may act on both the hypothalamus and the pituitary [9,22,[30][31].…”

“…The proposed mechanism by which ITT stimulates GH and ACTH, and AVP release is due to stimulation of GHRH and CRH and inhibition of SRIF release from the hypothalamus [2,6,7] and GHRP-2 may act on both the hypothalamus and the pituitary [9,22,[30][31]. In vivo, the GH-releasing activity of GHRP-2 increased BMI with a visceral obesity, although ITT test for GH secretion was not reexamined after one year later, because the ITT has a number of disadvantages, such as the potential for hypoglycemia-related adverse reactions which were sweating, palpitations and loss of consciousness as precoma shown in this subject [29].…”

“…stimulating hypothalamic releasing hormones (HRHs), including GHRH and CRH, and inhibiting SRIF release induced by hypoglycemia [2,6,7].…”

Hypothalamo–pituitary–adrenal axis response to coronary artery embolization: an ovine model of acute myocardial infarction

“…It was assumed that this negative feedback effect would have operated mainly at the pituitary level, otherwise CRH and AVP would also have been sup¬ pressed. Indeed the plasma AVP levels were so high in some individuals that tissue perfusion may have been further compromised (Crum et al 1990, Hader et al 1990). Because of the delay in presentation, even higher AVP levels may have occurred before admission to hospi¬ tal.…”