Contributory Roles of Distal Renal Sodium Transporters in NSAID-induced Sodium Retention / 대한신장학회잡지
Korean Journal of Nephrology
;
: 522-531, 2003.
Artículo
en Coreano
| WPRIM
| ID: wpr-51860
ABSTRACT
BACKGROUND:
Sodium retention occurs in some patients taking NSAIDs (nonsteroidal anti-inflammatory drugs). Although the renal effects of NSAIDs are predominantly mediated through the inhibition of prostaglandins synthesized by cyclooxygenase-2 (COX-2), the mechanisms of sodium retention are not clear at the sodium transporter levels in the kidney. Previous studies have shown that compensatory upregulation of COX-2 is induced in renal medulla by high salt intake and that NSAID-induced sodium retention may be transitory.METHODS:
To investigate whether renal sodium transporter abundances are altered by NSAID administration and whether renal sodium transporter abundances are affected by high salt intake or chronic NSAID administration, we performed an acute study treated with a single injection of diclofenac and another chronic study treated with 7 days' administration of DFU, a selective COX-2 inhibitor, using semiquantitative immunobotting from rat kidneys. Male Sprague-Dawley rats were divided into three groups in each study controls, NSAID treatment, and high-salt intake plus NSAID treatment. The control diet contained sodium 1 mmol/200 g BW/day, and the high-salt diet 10 mmol/200 g BW/day.RESULTS:
The acute study using diclofenac (100 mg/kg BW) increased the abundances of NKCC2 (by 73%) and ENaC-alpha (by 60%) in cortex and of NKCC2 (by 165%) and ENaC-alpha (by 91%) in outer medulla, in association with a significant decrease in urinary sodium excretion. The increased ENaC-alpha abundance was reversed by addition of high salt intake in both cortex and outer medulla. The chronic study using DFU (40 mg/kg/d for 7 days) showed no significant changes in distal renal sodium transporters except a decreased abundance of Na-K- ATPase alpha1-subunit (by 24%) in outer medulla. The addition of high salt intake decreased the abundances of ENaC-alpha (by 35%) and ENaC-beta (by 47 %) in outer medulla.CONCLUSION:
The abundances of thick ascending limb NKCC2 and collecting duct ENaC are altered in response to NSAID administration. It is suggested that NKCC2 & ENaC are contributory to NSAID- induced sodium retention and also have a compensatory role in high salt intake and chronic NSAID administration.
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Índice:
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Asunto principal:
Sodio
/
Regulación hacia Arriba
/
Prostaglandinas
/
Antiinflamatorios no Esteroideos
/
Diclofenaco
/
Ratas Sprague-Dawley
/
Adenosina Trifosfatasas
/
Dieta
/
Ciclooxigenasa 2
/
Extremidades
Límite:
Animales
/
Humanos
/
Masculino
Idioma:
Coreano
Revista:
Korean Journal of Nephrology
Año:
2003
Tipo del documento:
Artículo
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