Role of endogenous opioids in neurohypophysial function of man

Studies were carried out in normal human subjects to determine the effect of two narcotic antagonists, oxilorphan and butorphanol, on antidiuretic hormone (ADH) release. Oxilorphan given to eight subjects on ad libitum fluid intake resulted in a transient but significant increase in 24-h free water clearance and a decrease in urine osmolality. These changes were not accompanied by an increase in creatinine or solute excretion, and urinary ADH levels did not rise even though plasma osmolality rose significantly from 289.4 +/- 0.9 to 292.9 +/- 0.8 mosmol/kg. Treatment with oxilorphan did not interfere with the response to ADH infusion in water-loaded subjects. Both oxilorphan and butorphanol significantly elevated the plasma osmolality at which ADH release became evident after the infusion of hypertonic saline in water-loaded subjects. Oxilorphan suppressed urinary ADH excretion at the time of the osmotic threshold for ADH release in spite of the greater plasma osmolality. The data indicate that the narcotic antagonists are capable of inhibiting ADH release in man during ad libitum fluid intake and in response to an osmotic stimulus by elevating the osmotic threshold for ADH release. It is concluded that narcotic antagonist inhibition of endogenous opioid action provides further evidence supporting a role for the brain opiates in the normal regulation of neurohypophysial hormone release in man.