Effects of morphine on the renal handling of sodium and lithium in conscious rats

The present study was carried out in order to assess the renal response to i.v. morphine in the rat, particularly the effects on tubular handling of sodium and lithium. Rats were prepared surgically with arterial and venous catheters and bladder cannulas. Clearance experiments and measurements of blood pressure and heart rate were carried out at least 4 days after surgery in unanesthetized animals. Intravenous administration of morphine (4 mg/kg b.wt.) caused a decrease in fractional sodium excretion, (at 90 min after injection, vehicle, 2.49 +/- 0.30% vs. morphine, 1.12 +/- 0.17%, P less than .05), in the absence of significant changes in systemic hemodynamics or glomerular filtration rate. This effect was prevented by pretreatment with naloxone. Enhanced proximal tubular reabsorption of sodium was considered as a possible explanation for the decrease in sodium excretion which followed morphine administration. Proximal tubular fluid reabsorption was estimated utilizing the lithium clearance method. Results indicated a reduction in fractional excretion of lithium by morphine administration (at 90 min, vehicle, 34.2 +/- 3.3% vs. morphine, 18.8 +/- 2.3%, P less than .05), which was also prevented by naloxone pretreatment. It is concluded that, under the present experimental conditions, morphine enhances tubular reabsorption of sodium by an opiate receptor-dependent mechanism and that this effect is, at least in part, localized in the proximal tubule.