Fluoxetine effect on kidney water reabsorption.
BACKGROUND
The pathogenesis of hyponatraemia caused by fluoxetine(Fx) use in the treatment of depression is not well understood. It has been attributed to a SIADH, although ADH-enhanced plasma level has not yet been demonstrated in all the cases reported in humans. This experiment aimed at investigating the effect of fluoxetine on the kidney and more specifically in the inner medullary collecting duct (IMCD).


METHODS
(1) In vivo study: (a) 10 rats were injected daily i.p. with 10 mg/kg fluoxetine doses. After 10 days, rats were sacrificed and blood and kidneys were collected. (b) Immunoblotting studies for AQP2 protein expression in the IMCD from injected rats and in IMCD tubules suspension from 10 normal rats incubated with 10(-7) M fluoxetine. (2) In vitro microperfusion study: The osmotic water permeability (P(f), mum/s) was determined in normal rats IMCD (n = 6), isolated and perfused by the standard methods.


RESULTS
In vivo study: (a) Injected rats with fluoxetine lost about 12% body weight; Na(+) plasma level decreased from 139.3 +/- 0.78 mEq/l to 134.9 +/- 0.5 mEq/l (p < 0.01) and K(+) and ADH plasma levels remained unchanged. (b) Immunoblotting densitometric analysis of the assays showed an increase in AQP2 protein abundance of about 40%, both in IMCDs from injected rats [control period (cont) 99.6 +/- 5.2 versus Fx 145.6 +/- 16.9, p < 0.05] and in tubule suspension incubated with fluoxetine (cont 100.0 +/- 3.5 versus 143.0 +/- 2.0, p < 0.01). In vitro microperfusion study fluoxetine increased P(f) in the IMCD in the absence of ADH from the cont 7.24 +/- 2.07 to Fx 15.77 +/- 3.25 (p < 0.01).


CONCLUSIONS
After fluoxetine use, the weight and plasma Na(+) level decreased, and the K(+) and ADH plasma levels remained unchanged, whereas the AQP2 protein abundance and water absorption in the IMCD increased, leading us to conclude that the direct effect of fluoxetine in the IMCD could explain at least in part, the hyponatraemia found sometime after this drug use in humans.
Laboratório de Pesquisa Básica-LIM 12, Laboratórios de Investigação Médica-Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, Brazil.
Zenaide Providello
ZP
Moyses
Fausto Kigui
FK
Nakandakari
Antonio José
AJ
Magaldi
D000042:Absorption / Q000187:drug effects; D000818:Animals; D018687:Antidepressive Agents, Second-Generation / Q000633:toxicity; D051399:Aquaporin 2 / Q000096:biosynthesis / Q000187:drug effects; D015153:Blotting, Western; D004591:Electrophoresis, Polyacrylamide Gel; D005473:Fluoxetine / Q000633:toxicity*; D007010:Hyponatremia / Q000139:chemically induced / Q000378:metabolism*; D007685:Kidney Tubules, Collecting / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D012964:Sodium / Q000097:blood*; D014867:Water / Q000378:metabolism*
D018687:Antidepressive Agents, Second-Generation; C496025:Aqp2 protein, rat; D051399:Aquaporin 2; D005473:Fluoxetine; D014867:Water; D012964:Sodium