Kappa-opioid agonist induced diuresis. Is it mediated by a blood-borne factor of adrenomedullary origin?

Intravenous administration of the kappa-opioid agonists U50488H, tifluadom, and ethylketocyclazocine induced a characteristic diuresis in conscious, intact, saline-loaded rats. Naloxone pretreatment antagonized U50488H-induced diuresis. The diuretic response to the kappa-opioid agonists was significantly attenuated in adrenal demedullated rats. However, basal urine output, the diuretic response to furosemide, and the antidiuretic response to the mu-opioid agonist buprenorphine were unaffected. Transfusion studies established that 1 mL of blood, from intact donor rats treated with U50488H, induced a diuretic response when administered to intact or demedullated recipient rats, whether or not the recipients had been pretreated with naloxone. However, blood from demedullated rats treated with U50488H was unable to induce diuresis in intact or demedullated recipients. The results indicate that kappa-opioid agonist induced diuresis appears to be mediated by a nonopioid blood-borne "diuretic factor" of adrenomedullary origin and that this factor might be responsible for the dependence of the diuretic response upon an intact and functional adrenal medulla in conscious rats.