To evaluate the rate of production and turnover of antidiuretic hormone (ADH), it is essential to know its volume of distribution. Our previous paper (1), and those in the literature (2-4), have suggested that this volume approximates the plasma volume, and most authors have explained this as the result of binding of ADH to plasma proteins. In the accompanying study (1) on the physiology of ADH in man, we were unable to demonstrate the binding of the hormone to plasma proteins using in vitro ultrafiltration and dialysis techniques. Despite this, the volume of distribution of arginine-vasopressin, calculated from the injected dose and the extrapolated zero time concentration in the plasma, was only 2.5 % of the body weight, a volume significantly less than plasma volume. We concluded, however, that under the circumstances of these experiments the volume calculated from the extrapolation technique was erroneously low. In the same study we found that the turnover rate of both endogenous and exogenous ADH (arginine-vasopressin) in humans was related to the state of hydration. Three days of dehydration significantly accelerated while a comparable period of sustained over hydration slowed the observed normal turnover rate.The present study was undertaken in an effort to determine the true volume of distribution in animals, using a constant infusion technique, and to determine whether the fractional turnover rate * Submitted for publication December' 18, 1963; ac- was truly influenced by the state of hydration per se or by the different levels of circulating ADH resulting from the various states of hydration.
MethodsThe fractional turnover rate and volume of distribution of endogenous and exogenous ADH Dog experiments. 1) The disappearance curve of endogenous ADH and injected arginine-vasopressin in the water-loaded animal. Four trained female dogs were deprived of fluids for 12 hours. At the start of the experiment a sample of blood was drawn from an indwelling needle in the foreleg vein, and the animals were hydrated by stomach tube with 800 to 1,000 ml of tap water (5% of body weight). This state of hydration was maintained by a continuous iv infusion of 2.5% glucose in 0.45% sodium chloride at a rate equivalent to urine output. At suitable intervals blood samples were obtained for ADH determination. Timed urine specimens were collected by an indwelling catheter. The osmolality of the urine samples was measured by freezing point depression, using a Fiske osmometer.1 ADH was assayed by a modification of the bioassay of Heller and Stulc (1, 5). After maximal water diuresis was attained, two of the dogs were injected intravenously with 2.5 mU of synthetic arginine-vasopression,2 and its disappearance from the circulation was followed. From these data the fractional turnover rates and apparent volume of distribution were calculated.