The Renal Response to Sustained Administration of Vasopressin and Water in Man*

An evaluation of the effects of prolonged administration of vasopressin on water and electrolyte metabolism was made in 5 studies on 4 human subjects. In subjects receiving a high fluid intake, an initially rapid expansion of total body water associated with an excessive urinary excretion of sodium was observed. Ultimately, however, urinary osmolality declined, daily urinary output rose, and body water balance was re-attained. Concomitantly, excessive natriuresis and net loss of body sodium ceased, despite the presence of an expanded body fluid volume. Although administration of vasopressin and a high fluid intake was continued, a new steady state was achieved. This was characterized by persistent overhydration and hyponatremia. It is suggested that duration of the overhydrated state is a critical factor in determining the development of a reduced renal responsiveness to vasopressin. This response was never observed prior to the seventh day of vasopressin administration, and in two studies occurred when only slight overhydration was present. A clinically significant degree of sodium depletion was not produced by this procedure. The persistent hyponatremia was primarily the result of water retention. The present data provide certain criteria for the clinical evaluation of hyponatremic states in which sustained excessive secretion of antidiuretic hormone is suspected as the etiologic mechanism.