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 mumol/kg, and reached a maximum of about 85% of the stimulated control at a dose of 2.2 mumol/kg.
Diprenorphine also inhibited the
vasopressin response to an osmotic or a hypotensive stimulus, but the effect was less complete (approximately 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 mumol/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.