Dysregulation of renal cyclooxygenase-2 in rats with lithium-induced nephrogenic diabetes insipidus

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.