THE EFFECT OF THE NONSELECTIVE OPIOID ANTAGONIST DIPRENORPHINE ON VASOPRESSIN SECRETION IN THE RAT

Although endogenous opioids are thought to be involved in the regulati on of vasopressin secretion, their precise role is unclear. We studied the effect of the potent nonselective opioid antagonist diprenorphine on the vasopressin response to osmotic (hypertonic saline, ip), hypov olemic (polyethylene glycol, ip), and hypotensive (sodium nitroprussid e, sc) stimuli in male rats. We found that diprenorphine sc produced a time- and dose-dependent inhibition of the plasma vasopressin respons e to the hypovolemic stimulus. This inhibition was greatest 30 min aft er injection of the drug, but lasted for at least 4 h, was evident at doses as low as 0.0022 mu mol/kg, and reached a maximum of about 85% o f the stimulated control at a dose of 2.2 mu mol/kg. Diprenorphine als o inhibited the vasopressin response to an osmotic or a hypotensive st imulus, but the effect was less complete (similar to 50%), required 10 0-fold higher doses of the drug, and appeared to be bimodal. The poten t kappa(1)-selective opioid agonist U-50,488H also suppressed the vaso pressin response to these stimuli, but the effect was not selective fo r hypovolemia, and the doses required (0.135-13.5 mu mol/kg) were abou t 10- to 100-fold higher than those of diprenorphine. We postulate, th erefore, that diprenorphine potently and preferentially inhibits the v asopressin response to an acute hypovolemic stimulus by antagonizing t he effect of some endogenous opioidergic system critical in the volume control system.