Contributory Roles of Distal Renal Sodium Transporters in NSAID-induced Sodium Retention.
- Author:
Gheun Ho KIM
1
;
So Young KIM
;
Kwon Wook JOO
;
Un Sil JEON
;
Jang Won SEO
;
Jay Wook LEE
;
Jin Suk HAN
Author Information
1. Department of Internal Medicine, College of Medicine, Hallym University Hangang Sacred Heart Hospital, Seoul, Korea. kimgh@hallym.or.kr
- Publication Type:Original Article
- Keywords:
Nonsteroidal anti-inflammatory drug;
Sodium retention;
NKCC2;
ENaC;
Kidney
- MeSH:
Adenosine Triphosphatases;
Animals;
Anti-Inflammatory Agents, Non-Steroidal;
Cyclooxygenase 2;
Diclofenac;
Diet;
Extremities;
Humans;
Kidney;
Male;
Prostaglandins;
Rats;
Rats, Sprague-Dawley;
Sodium*;
Up-Regulation
- From:Korean Journal of Nephrology
2003;22(5):522-531
- CountryRepublic of Korea
- Language:Korean
-
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.
