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 micrograms/kg of the antagonist, b. after injection of placebo (0.9% NaCl). Plasma ACTH levels during AVP infusion rose from 17.2 +/- 1.6 ng/l (3.8 +/- 0.35 pmol/l) to 31.7 +/- 4.2 ng/l (7.0 +/- 0.92 pmol/l) at 40 min after injection of the antagonist, the difference to the control-group (increment from 16.5 +/- 1.2 ng/l (3.6 +/- 0.26 pmol/l) to 41.8 +/- 3.5 ng/l) (9.2 +/- 0.77 pmol/l) being significant (p less than 0.05). Peak plasma cortisol levels were 323 +/- 42 and 529 +/- 52 nmol/l, respectively (p less than 0.05). We then tested the compound in the same subjects during an insulin-induced hypoglycemia; 30 min after administration of 10 micrograms/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 +/- 19 nmol/l with antagonist and 469 +/- 90 nmol/l with placebo, p less than 0.05) during insulin-induced hypoglycemia.(ABSTRACT TRUNCATED AT 250 WORDS)