EFFECTS OF 8-LYSINE-VASOPRESSIN AND SYNTHETIC ANALOGUES ON RELEASE OF ACTH

Abstract

ABSTRACT Two synthetic analogues of vasopressin, [N-α-triglycyl-8-lysine]-vasopressin (GVP) and [1-deamino-8-D-arginine]-vasopressin (DDAVP), with a pronounced and long-lasting pressor and antidiuretic action respectively, were given to healthy volunteers in order to investigate whether the ACTH-releasing ability of vasopressin, reflected by plasma cortisol increase, is related to its pressor or to its antidiuretic effect. The effecti'veness of 3 different intravenous doses of [8-lysine]-vasopressin (LVP) in causing release of ACTH was also studied, and the responses compared with that caused by LVP given intramuscularly, the usually recommended route of administration. The lowest dose of LVP used in this study, 1 μg (0.25 IU) intravenously, caused a significant change of plasma cortisol. Doses of GVP with a pressor effect comparable to that of 8 μg of LVP did not affect the plasma cortisol level significantly in spite of obvious pressor effects. Nor did DDAVP in doses which should exert a maximal antidiuretic effect (4 and 16 μg) increase the plasma cortisol level. In 2 out of 10 subjects, 40 μg of LVP (10 IU) given intramuscularly failed to give a rise in plasma cortisol exceeding 5μg/100 ml, which is generally required for regarding the response as normal, and also 16 μg (4 IU) of LVP intravenously failed to produce a response reaching this level in 1 out of 12 subjects. It is concluded that the ACTH-releasing ability of vasopressin is neither associated with its pressor nor with its antidiuretic action. The finding that normal subjects can have a low response to vasopressin reduces its value for testing the function of the hypothalamic-pituitary – adrenocortical system.