Abstract
Hyponatremia has been reported in the treatment with Fluoxetine (Fx), but the pathogenesis of this effect is not well known. This has been attributed to an inappropriate antidiuretic hormone secretion although the vasopressin enhanced plasma level has not been demonstrated yet. Thus, this experiment was designed to investigate if Fx has a direct effect in the IMCD from normal rats. Two kinds of experiments were carried out: 1) “in vivo” study- 10 rats were supplied daily with i.p. injections of Fx 10 mg/kg. After five days, the rats were sacrificed and blood was collected. 2) “in vitro” study -The osmotic water permeability (Pf x [micro]m.s-1), was determined at 37°C and pH 7.4,in normal rats IMCD (n=6) perfused and bathed with Ringer/HCO3. Fx (10–7 M) was added to the bath fluid. The results from the “in vivo” study showed that the weight decreased from 179±3.4g to 158±3.0g(p<0.001); the urinary volume decreased from 14,5±1.5ml/12h to 7.5±0.7ml/12h(p<0.01); the Na+ plasma level decreased from 140.0±0.78mEq/l to 134.7±0.5mEq/l(p<0.01) and the K+ and the ADH plasma level remained unchanged. The data showed that Fx increased the Pf in IMCD in absence of vasopressin from the control period- 22.6±10.0 x [micro]m.s-1 to Fx- 55.9±18.9 x[micro] m.s-1 (p<0.05). In summary, our data revealed that after Fx supply, weight, urinary volume, and plasma Na+ level decreased significantly and the plasma ADH level remained unchanged, whereas the water absorption in IMCD increased, leading us to conclude that the direct effect of Fx in the IMCD, increasing Pf in absence of vasopressin, could account for the hyponatremia produced by this drug in depressed elderly. LIM-HCFMUSP/FFMUSP/FAPESP/CNPq.
Published Version
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