THE RÔLE OF THE NEUROHYPOPHYSIS OF THE DOG IN DETERMINING URINARY CHANGES, AND THE ANTI‐DIURETIC ACTIVITY OF URINE, FOLLOWING THE ADMINISTRATION OF SODIUM CHLORIDE OR UREA

1. The urine of dogs given 60‐100 ml. of 3‐5 per cent. sodium chloride by stomach tube contained a substance causing inhibition of water diuresis on intravenous injection into a second dog. No such inhibition was produced by the urine of dogs given the same dose of sodium chloride after operative destruction of the neurohypophysis. 2. The urine of normal dogs given 200‐300 ml. of 0·75‐0·9 per cent. sodium chloride or 10 g. of urea in 100 ml. of water contained no anti‐diuretic activity. 3. Investigation was made of the excretion of antidiuretic activity in the urine during and after the intravenous infusion of pituitary (posterior lobe) extract. When infusion at a constant rate was maintained for 20 min. or more, a steady state was attained in which anti‐diuretic activity appeared in the urine at a rate 7‐15 per cent. of the rate of infusion. Antidiuretic activity was not detected in urine collected 20 min. or more after the end of infusion of 1 mU per min. lasting one hour. 4. When a fixed dose of sodium chloride (3 g.) was given by stomach tube in solutions of volume and concentration between 353 ml. of 0·85 per cent. and 100 ml. of 3 per cent., and by intravenous infusion of 20 ml. of 15 per cent., the antidiuretic activity of the urine increased with increasing strength of the solution. Assay of the antidiuretic activity of the urine showed the excretion of less than 0·013, 0·03–0·07 and 0·10–0·14 mU per min. of antidiuretic activity in the urine of dogs given the three solutions above. 5. From the results of 3 and 4 it was deduced that the rate of release of hormone from the neurohypophysis of dogs given the solutions listed in 4 was less than 0·12, 0·5‐0·6 and 1·0–1·4 mU per min., the release increasing with increasing strength of the solution administered. 6. Whether sodium chloride was given in solution hypertonic or isotonic to the body fluids, in normal animals or in animals after operative destruction of the neurohypophysis, the amount of chloride excreted per min. increased equally. The rate of excretion of chloride was thus not determined by the release of hormone from the neurohypophysis; it was not altered by infusion of pituitary (posterior lobe) extract in physiological amounts. 7. When sodium chloride was given to normal dogs in solution hypertonic to the body fluids (1·7 per cent. or stronger), chloride was excreted in urine of chloride concentration 0·25–0·3 M or more; but after section of the supraoptico‐hypophyseal tracts, or when salt was given in isotonic solution, the chloride was excreted in a larger volume of urine of low chloride concentration (less than 0·15 M). The hormone of the neurohypophysis thus limited water loss and so determined the concentration of chloride during its excretion. Removal of the posterior lobe produced less disturbance of this function than section of the supraoptico‐hypophyseal tracts. 8. When extract of the posterior lobe was infused or hormone was released endogenously at rates greater than 0·25 mU per min., maximal conservation of water was attained, and increased rates of infusion or release did not alter the volume or composition of the urine. This rate of release was produced by an increase of about 5 per cent. in the chloride content of the blood. At rates up to 0·25 mU per min. the chloride concentration of the urine, and so the conservation of water, increased with increasing rates of release or infusion of hormone. 9. Less than 0·12 mU per min. of hormone was released from the neurohypophysis following the administration of 10 g. of urea in 100 ml. of water. The rate of excretion of urea was not altered by infusion of extract of the posterior lobe or after section of the supraoptico‐hypophyseal tracts, but, as with chloride, the presence of the neurohypophyseal hormone determined the volume and concentration of the urine during the excretion of the urea. Infusion of extract of the posterior lobe at 0·2 mU per min. was adequate to ensure the excretion of urea in urine of minimal volume and maximal urea concentration. 10. These results, like the facts concerning water diuresis, may be explained without postulating any effect of the neurohypophyseal hormone other than that of determining the selective reabsorption of water in the renal tubules.