Croonian Lecture - The antidiuretic hormone and the factors which determine its release

When water is given under specified conditions to the living dog, there is a lag of 15 min. between the peak of the animal's water load and the maximum rate of water excretion by the kidney. The diuresis is inhibited by emotional stress, the inhibition being of post-pituitary origin and itself suppressed by an immediately preceding injection of adrenaline or tyramine. Reasons are given for the view that this action of adrenaline is independent of any accompanying increase in arterial pressure or cerebral blood flow. The intracarotid injection (short period, 5 to 20 sec.) of 'hypertonic' solutions of sodium chloride (but not of urea) causes a similar inhibition, the response being diminished by some 90% after removal of the posterior lobe. The response to sodium chloride is shown to be osmotically determined, and the term 'osmoreceptors' has therefore been introduced as descriptive of the autonomic receptive elements with which the neurohypophysis is functionally linked. The receptors are somewhere in the vascular bed of the internal carotid artery. The results of long-period (10 and 40 min.) intracarotid infusions and of the short-period injections, show that the osmoreceptors are freely permeable to urea, less freely permeable to dextrose and relatively impermeable to sodium chloride and sucrose. The local increase in osmotic pressure required in the 40 min. infusions (unilateral) to reduce the urine flow during water diuresis to about 10% of its maximum, is some 2% only; and assay of such response shows it to have a post-pituitary extract equivalence of $1\mu \text{U/sec.}$ $(0.5\times 10^{-9}$ $\text{g./sec.}$ in terms of the standard powder). These facts give an intelligible interpretation to the time-lag between the peak of the water load and the peak of diuresis. Water diuresis, therefore, is fitly and accurately described as a condition of physiological diabetes insipidus, the antidiuretic secretion of the neurohypophysis being a hormone in the sense that its liberation is continually governed by the concentration of sodium chloride, and of other osmotically active substances, in the arterial plasma.