Measurement of the Osmotic Threshold for Vasopressin Release in Human Subjects, and Its Modification by Cortisol1

Abstract

The level of plasma osmolality at which hydrated human subjects 1st respond to an intravenous infusion of 5% saline with a statistically significant fall in free water clearance (without a fall in osmolal clearance or creatinine excretion) has been called the osmotic threshold for vasopressin (ADH) release. The mean osmotic threshold in 8 normal subjects was found to be 289.51 [plus or minus] (SD) 2.35 mOsm/kg and to rise by 3.72 [plus or minus] 0.53 (SE) mOsm/kg after treatment with 100 mg cor-tisol daily, by mouth, for 2 days (p < .001, by t test for paired comparisons). In 6 normal subjects, the osmotic threshold was elevated by 2.57mOsm/kg [plus or minus] 0.63 (SE) by infusing cortisol intravenously with the hypertonic saline (p< .01). Thus, both acute intravenous administration of cortisol over the space of less than 2 hr and the oral administration of the steroid for 2 days raised the level to which the plasma osmolality had to be elevated in order to stimulate ADH release. Cortisol was shown neither to delay nor to diminish the renal response to infused or injected arginine vasopressin, implying that the effects of cortisol on the osmotic threshold did not result from changes in the renal responses to endogenously release vasopressin. Cortisol infusion prolonged the duration of the 5% NaCl infusion from its onset until the attainment of the osmotic threshold from 68.3 to 99.3 min. (p < .01). The best explanation of this finding and the other data reported appears to be that cortisol delays ADH release in response to a rising plasma osmolality, perhaps by increasing the osmolar content and thus the size of the hypothalamic "osmoreceptors," or by expanding the plasma or extracellular fluid volum.