EFFECT OF MORPHINE ON URINE OUTPUT - POSSIBLE ROLE OF ATRIAL-NATRIURETIC-FACTOR

We examined the possible role of atrial natriuretic factor (ANF) in mo rphine-induced diuresis. Morphine (20 mug/20 mul) administered intrace rebroventricularly (i.c.v.) in conscious, normally hydrated Sprague-Da wley rats significantly increased urine output from 0.22 +/- 0.16 ml/h /rat to 2.07 +/- 0.46 ml/h/rat, 3 h after injection. Morphine injectio n also significantly increased the plasma ANF level to a maximum of 36 4 +/- 46 pg/ml compared to control animals (33 +/- 7 pg/ml) in which 2 0 mul of saline was injected i.c.v. (P < 0.001). This peak increase oc curred 1 h after morphine administration, however, it continued to rem ain significantly elevated (171 +/- 36 pg/ml vs. 39 +/- 8 pg/ml in con trol animals; P < 0.001) 2 h later. The maximal diuresis observed 3 h after administration of morphine i.c.v. was abolished by pretreatment of the animals with 0.8 mg of naloxone given intravenously (i.v.) and also by anti-rat ANF serum (0.4 ml i.v.). A short, transient increase in blood pressure, occurred 2-5 min after morphine administration, but it is unlikely that this increase accounted for the increase in plasm a ANF. We conclude that he diuresis induced by i.c.v. administration o f morphine is due to enhanced release of ANF.