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Since the description of antidiuretic hormone (1) and the factors which influence its release from the neurohypophysis (2), renal investigators have been interested in correlating physiological and clinical situations to the plasma levels of this hormone. However, the accurate measurement of antidiuretic activity in human plasma has proved difficult because of the lack of a sensitive method of bioassay and the extremely low concentrations of antidiuretic hormone (ADH) which are present in peripheral blood. Further interest in measuring antidiuretic activity in human plasma was prompted by two factors: 1) the recent development of an improved method of bioassay of antidiuretic hormone in mammalian plasma (3, 4), and 2) an opportunity to obtain blood from the superior vena cava where dilution and inactivation of antidiuretic hormone were considered to be minimal. The purpose of this investigation was to employ procedures calculated to stimulate the secretion of ADH in normal human subjects and to correlate plasma levels of antidiuretic activity with free water clearance. Three patients with diabetes insipidus were also studied. METHODS The assay method for plasma antidiuretic activity has been previously described (4) and utilizes rats anesthe-tized with ethanol, under constant water load; a minor modification which has been introduced involves the injection into each assay animal of fixed amounts of standard vasopressin solutions, the antidiuretic response (instead of the dose of standard vasopressin solution administered) now being related to the rat's body weight. Plasma samples and standard solutions of aqueous vaso-pressin (Pitressin, Parke, Davis & Co., Lot no. 3-161-lOW 107GA) were administered intravenously and in each instance the volume of plasma or standard injected was 0.7 ml; 0.1 ml of heparin saline solution (1: 100) was used to wash in the test material. In all cases the human plasma was injected into the rat within 12 minutes after blood withdrawal. The same rats were used for measurement of plasma antidiuretic activity and standard vasopressin solutions except in rare instances in which an animal developed hematuria or oliguria. The rats' urine was collected at 10-minute intervals and the degree of antidiuresis was expressed as an anti-diuretic index per 100 g of rat body weight; i.e., the percentage change in urine specific gravity calculated from the average of two 10-minute samples preceding injection and the average of two 10-minute samples immediately following injection. The antidiuretic activity of the plasma samples was determined by relating the antidiu-retic index obtained with plasma to …

PLASMA ANTIDIURETIC ACTIVITY AND FREE WATER CLEARANCE FOLLOWING OSMORECEPTOR AND NEUROHYPOPHYSEAL STIMULATION IN HUMAN SUBJECTS