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The distribution, blood transport, and metabolic clearance of physiological concentrations of antidiuretic hormone were studied in 10 hydrated normal subjects with radioiodinated arginine vasopressin (125I-AVP). At 37 degrees C no binding of 125I-AVP to plasma proteins could be demonstrated, but some metabolites were associated with plasma proteins. 125I-AVP was rapidly distributed into a space approximating the extracellular fluid volume. Metabolic breakdown products became demonstrable within minutes after injection. The mean metabolic clearance rate of 125I-AVP was 4.1 ml/min/kg and the mean plasma half-life 24.1 min. Renal clearance had a mean value of 80 ml/min and accounted for 27% of the total metabolic clearance. It is concluded that in man antidiuretic hormone circulates as a free (non-protein bound) peptide, diffuses readily into the extracellular fluid space, and is metabolized within minutes. A plasma half-life of 24 min is consistent with the duration of antidiuresis after hormone administration or release.

Trichloroacetic acid extracts of plasma were fractionated on a CG-50 resin column and the 50% acetic acid eluents chromatographed on silicic acid-impregnated glass paper in butanol-acetic acid-water. The specific arginine vasopressin (AVP) zone was eluted and assayed for antidiuretic activity in the diuretic rat. Thioglycolate inactivation was used to confirm AVP activity. Recovery of as little as 4 muU AVP per ml plasma ranged between 80 and 90%. In normal subjects after an overnight fast, plasma AVP ranged between 2.5 and 10.0 muU per ml. AVP secretion was inhibited by hemodilution and stimulated with nicotine and hypertonic saline. Plasma AVP was absent in patients with diabetes insipidus even after neurohypophyseal stimulation. Plasma AVP was abnormally elevated during mild dehydration and remained above the normal range despite hemodilution in patients with untreated adrenocortical insufficiency demonstrating a delayed water diuresis. Glucosteroid therapy lowered plasma AVP to normal in dehydrated patients. A normal diuretic response to hydration was accompanied by a fall in plasma AVP to zero in steroid-treated patients. These findings suggest that hypersecretion of AVP may play an important role in the abnormal water metabolism of adrenocortical insufficiency and that the glucosteroids promote normal water diuresis by inhibiting the secretion of AVP from the neurohypophysis.