Effect of Morphine on Urine Output: Possible Role of Atrial Natriuretic Factor

We examined the possible role of atrial natriuretic factor (ANF) in morphine-induced diuresis. Morphine (20 micrograms/20 microliters) administered intracerebroventricularly (i.c.v.) in conscious, normally hydrated Sprague-Dawley 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 injection also significantly increased the plasma ANF level to a maximum of 364 +/- 46 pg/ml compared to control animals (33 +/- 7 pg/ml) in which 20 microliters of saline was injected i.c.v. (P < 0.001). This peak increase occurred 1 h after morphine administration, however, it continued to remain significantly elevated (171 +/- 36 pg/ml vs. 39 +/- 8 pg/ml in control 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 plasma ANF. We conclude that the diuresis induced by i.c.v. administration of morphine is due to enhanced release of ANF.