ROLE OF ATRIAL-NATRIURETIC-FACTOR, HEMODYNAMIC-CHANGES AND RENAL NERVES IN THE RENAL EFFECTS OF INTRAPERITONEAL MORPHINE IN CONSCIOUS RATS

The aim of the present study was to investigate the role of renal nerv es and atrial natriuretic factor (ANF) in the mechanisms responsible f or the diuresis and antinatriuresis induced by morphine in rats in a n ormal state of hydration. Male Wistar rats weighing 350-400 g were div ided into two groups: one group was subjected to bilateral renal dener vation, whereas the other consisted of sham-operated controls. The ani mals were placed in individual metabolic cages, and morphine (1.25, 2. 5, 5.0 or 10.0 mg/kg body weight) or vehicle (0.5 mi isotonic saline) was injected intraperitoneally. Urine was collected hourly for Ih befo re and 3 h after morphine injection. The lower doses of morphine (1.25 and 2.5 mg/kg body weight) induced a transient increase in urine outp ut (from 1.17+/-0.12 to 2.49+/-0.34 and from 0.78+/-0.08 to 1.71+/-0.1 8 mu l/min, respectively). The diuretic response to these doses was si milar in bilaterally denervated rats. Higher doses (5.0 and 10.0 mg/kg body weight) induced a marked but transient reduction in the urinary flow rate during the first hour (from 0.90+/-0.11 to 0.48+/-0.05 and f rom 1.37+/-0.17 to 0.45+/-0.08 mu l/min, respectively), followed by a delayed diuretic effect. The antidiuretic action of morphine was not o bserved in bilaterally denervated rats. In control rats, morphine indu ced a dose-dependent decrease in sodium excretion 1 h after administra tion, an effect that was blunted in the denervated group. The lower mo rphine doses (1.25 and 2.5 mg/kg body weight) elicited a transient inc rease in the glomerular filtration rate (GFR) in both control (from 1. 23+/-0.12 to 1.67+/-0.17 and from 1.28+/-0.14 to 2.41+/-0.18 ml/min) a nd bilaterally denervated rats (from 1.29+/-0.14 to 1.66+/-0.17 and fr om 1.18+/-0.22 to 1.72+/-0.19 ml/min), whereas the higher doses (5.0 a nd 10.0 mg/kg body weight) produced a marked, transient GFR decrease i n the controls (from 1.25+/-0.11 to 0.43+/-0.05 and from 1.13+/-0.17 t o 0.47+/-0.08 ml/min) and bilaterally denervated animals (from 1.48+/- 0.16 to 0.74+/-0.09 and from 1.22+/-0.15 to 0.73+/-0.06 ml/min), altho ugh the reduction was less pronounced with renal denervation. Morphine induced a transient, dose-dependent reduction in blood pressure (from 114+/-1 to 71+/-6 mm Hg at 10.0 mg/kg body weight) and a dose-depende nt elevation of plasma ANF. No differences in plasma ANF were observed between control and denervated animals under basal conditions (60+/-7 vs. 42+/-6 pg/ml) or after injection of 2.5 or 5.0 mg/kg of morphine (155+/-11 vs. 167+/-9 and 360+/-9 vs. 401+/-9 pg/ml, respectively). Ou r data suggest that the renal responses to intraperitoneal morphine ad ministration derive from the integration of several different actions: (1) increased ANF release; (2) decreased arterial pressure; (3) subse quent activation of renal sympathetic activity, and (4) the direct eff ect of morphine on tubular function.