Capacity of the Neurohypophysis To Release Vasopressin¹

Within a few minutes after reduction of blood pressure of dogs to 50 mm Hg by bleeding there is a rapid discharge of vasopressin (ADH) into the blood. In the presence of a maintained stimulus of hemorrhagic hypotension, the initial secretory response is not sustained beyond the first few minutes of hemorrhage. Reinfusion of the shed blood after 30 min of hemorrhage restored the arterial blood pressure and the blood ADH concentration to relatively normal values. A second hemorrhage 1 hr later failed to raise the concentration of blood ADH beyond the level observed just prior to blood reinfusion. Direct analysis of the pituitary glands showed that the decline in the release of ADH during hemorrhage could not be attributed to exhaustion of the pituitary content of ADH. Furthermore, ADH release did not appear to be a simple function of the total hormone content of the gland. Nevertheless, this attenuation of ADH release appears to reside in part at the level of the pituitary. Pituitaries taken from bled dogs released much less ADH in vitro in response to electrical or K+ stimulation than pituitaries from non-bled animals. Morphological and functional criteria incated that the neurosecretory cells had not been damaged during hemorrhage. Electron microscopymicroscopy studies showed that the fine structure of the neural lobe from intact and bled dogs was similar in appearance. Likewise, no significant differences have been detected in the morphology of isolated neural lobes incubated in vitro in media containing either 5.6 or 56 mM K+. Isolated pituitaries (from non-bled dogs) stimulated continuously in vitro also showed a progressive decline in ADH secretion; the secretion rate decreased more rapidly than did the pituitary content of hormone. The decline in hormone secretion was not due to extensive membrane depolarization per se but appeared to depend upon the prior secretion of ADH. Analogous results were obtained under circumstances (carotid perfusion and section of the vagi) in which hemorrhage fails to elicit an appreciable discharge of ADH. It is suggested as a working hypothesis that the pool of neurohypophysial ADH is heterogeneous and that there is a “readily releasable” pool which comprises about 10- 20 % of the total hormone content of the gland. Once this “readily releasable” pool of hormone has been discharged, the neurohypophysis continues to release vasopressin in response to appropriate stimuli, but at a greatly reduced rate. (Endocrinology81 : 755, 1967)