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

Although endogenous opioids are thought to be involved in the regulation 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), hypovolemic (polyethylene glycol, ip), and hypotensive (sodium nitroprusside, sc) stimuli in male rats. We found that diprenorphine sc produced a time- and dose-dependent inhibition of the plasma vasopressin response to the hypovolemic stimulus. This inhibition was greatest 30 min after 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% of the stimulated control at a dose of 2.2 mu mol/kg. Diprenorphine also inhibited the vasopressin response to an osmotic or a hypotensive stimulus, but the effect was less complete (similar to 50%), required 100-fold higher doses of the drug, and appeared to be bimodal. The potent kappa(1)-selective opioid agonist U-50,488H also suppressed the vasopressin response to these stimuli, but the effect was not selective for hypovolemia, and the doses required (0.135-13.5 mu mol/kg) were about 10- to 100-fold higher than those of diprenorphine. We postulate, therefore, that diprenorphine potently and preferentially inhibits the vasopressin response to an acute hypovolemic stimulus by antagonizing the effect of some endogenous opioidergic system critical in the volume control system.