Cyclooxygenase-2 inhibitor preserves medullary aquaporin-2 expression and prevents polyuria after ureteral obstruction.
OBJECTIVE
Renal obstruction causes impairment of urinary concentrating ability, partly by decreasing aquaporin-2 (AQP-2) water channel level in the collecting ducts. We reported previously that ureteral obstruction induced cyclooxygenase-2 (COX-2) in the medullary collecting duct cells by increased mechanical stretch. In this study we investigated whether AQP-2 decrease after obstruction was regulated by COX-2.


METHODS
Sprague-Dawley rats were subjected to bilateral ureteral obstruction for 24 to 48 hours. During obstruction rats were given NS398, a COX-2 specific inhibitor, by oral gavage (2 mg/kg per day). COX-2 and AQP-2 levels were assessed in the inner medulla using Western blot. Urine output was measured after releasing obstruction to assess the degree of polyuria.


RESULTS
With obstruction COX-2 protein levels increased and AQP-2 levels decreased in the inner medulla. Corresponding to the loss of AQP-2, urine output increased 4.2-fold after obstruction. The obstructed rats receiving NS398 exhibited significant preservation of AQP-2 level (72% of control), as well as significant normalization of urine output. The sham operated rats receiving NS398 exhibited an increased amount of AQP-2 protein level.


CONCLUSIONS
These findings suggest that COX-2 mediated prostaglandin has an important role in the down-regulation of AQP-2 water channel level in the medullary collecting duct cells after ureteral obstruction.
Cheng
Xu
X
Department of Urology, Michigan Urology Center, University of Michigan Medical School, Ann Arbor, Michigan 48109-0330, USA.
Zhang
Hongyu
H
Lee
Hyung-Lae
HL
Park
John M
JM
D000818:Animals; D051399:Aquaporin 2 / Q000096:biosynthesis*; D051546:Cyclooxygenase 2 / Q000502:physiology*; D052246:Cyclooxygenase 2 Inhibitors / Q000494:pharmacology*; D007679:Kidney Medulla / Q000187:drug effects* / Q000378:metabolism*; D009578:Nitrobenzenes / Q000494:pharmacology*; D011141:Polyuria / Q000209:etiology / Q000517:prevention & control*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013449:Sulfonamides / Q000494:pharmacology*; D014517:Ureteral Obstruction / Q000150:complications / Q000378:metabolism*
D051399:Aquaporin 2; D052246:Cyclooxygenase 2 Inhibitors; D009578:Nitrobenzenes; D013449:Sulfonamides; C080955:N-(2-cyclohexyloxy-4-nitrophenyl)methanesulfonamide; D051546:Cyclooxygenase 2