Electrolyte Blood Press.  2007 Dec;5(2):68-74. 10.5049/EBP.2007.5.2.68.

Dysregulation of Renal Cyclooxygenase-2 in Rats with Lithium-induced Nephrogenic Diabetes Insipidus

• Kwon TH

• KMID: 2052288
• DOI: http://doi.org/10.5049/EBP.2007.5.2.68

Abstract

This study aimed to examine whether the expression of major prostaglandin E2 (PGE2) synthesis enzyme, cyclooxygenase-2 (COX-2), is changed in the kidneys of the rats with lithium-induced nephrogenic diabetes insipidus (Li-NDI). Sprague- Dawley rats treated with lithium for 4 weeks were used as the NDI model and expression of renal COX-2 was determined by immunoblotting and immunohistochemistry. In Li-NDI where urine output was markedly increased and urine osmolality was significantly decreased, COX-2 expression in the inner medulla was decreased (28% of control), while it increased 18-fold in the cortex and outer medulla. Consistent with this, labeling intensity of COX-2 in macula densa region was increased, whereas it was decreased in the interstitial cells in the inner medulla, indicating a differential regulation of COX-2 between the cortex and inner medulla in Li-NDI. Accordingly, urinary PGE2 excretion was significantly increased in Li-NDI. In conclusion, there is a differential regulation of COX-2 between cortex and inner medulla in Li- NDI and urinary PGE2 excretion is increased in Li-NDI, possibly due to an increased renal production. This may suggest that increased renal production of PGE2 could play a role in modulating water reabsorption in the renal collecting duct in Li-NDI.

MeSH Terms

Animals
Aquaporins
Cyclooxygenase 2*
Diabetes Insipidus, Nephrogenic*
Dinoprostone
Immunoblotting
Immunohistochemistry
Kidney
Lithium
Osmolar Concentration
Prostaglandins
Rats*
Aquaporins
Cyclooxygenase 2
Dinoprostone
Lithium
Prostaglandins

Figure

• 

  Fig. 1 Changes of urine output, urine osmolality, and urinary prostaglandin E2 (PGE2) excretion. Rats with lithium-induced nephrogenic diabetes insipidus demonstrated increased urine output, decreased urine osmolality, and increased urinary PGE2 excretion, compared with the controls. *p<0.05.

• 

  Fig. 2 Semiqunatitative immunoblotting demonstrated that chronic LiCl treatment markedly increased the expression of cyclooxygenase-2 (COX-2) in the kidney cortex and outer medulla (Cor+OM) compared with controls (Con, A and B), whereas chronic LiCl treatment decreased the expression of COX-2 in the kidney inner medulla (IM, C and D). *p<0.05.

• 

  Fig. 3 Immunoperoxidase labeling of cyclooxygenase-2 (COX-2) demonstrated an increased COX-2 labeling in the macula densa of the cortical thick ascending limb in rats with lithium-induced nephrogenic diabetes insipidus (indicated as MD in A) compared with the controls (B). In the inner medulla, weak but distinct COX-2 labeling was observed in a characteristic perinuclear pattern in inner medullary interstitial cells of the kidneys from control rats (arrows in D), whereas no or very weak labeling of COX-2 was seen in the inner medulla of the kidneys from Li-treated rats (arrows in C). Glo, glomerulus; IMCD, inner medullary collecting duct; MD, macula densa.

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