Physiologic Studies of Antidiuretic Hormone by Its Direct Measurement in Human Plasma *

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Abstract
A sensitive and re -producible bioassay for antidiuretic hormone (ADH) in mammalian plasma was developed utilizing the hydrated ethanol-anesthetized rat. Bladder exteriorization and a continuous intravenous infusion of hypo-tonic solution made it possible to maintain constant water diuresis. With this preparation as little as 0. 25 [mu]U of ADH/ml could be detected. At this plasma level a maximal water diuresis was always observed. ADH disappeared from the circulation of water-loaded normal humans in an exponential manner with a half life of 16 to 17 minutes. The latter was increased by chronic overhydration and decreased by chronic dehydration. Calculation of the apparent volume of distribution of exogenous ADH from the extrapolated zero time concentration in the plasma gave a value of approximately 2.5% of the body weight. It was felt that this technique under-estimated the true volume of distribution and that the latter more closely approximated the plasma volume. Despite this, no binding of ADH to plasma proteins could be demonstrated. The peak of maximal water diuresis coincided with, or may even have preceded, the attainment of zero (0.< 25 [mu]U/ml) ADH levels in the plasma.