Cyclooxygenase type 2 is increased in obstructed rat and human ureter and contributes to pelvic pressure increase after obstruction.
Prostanoids exert physiological effects on ureteral contractility that may lead to pressure changes and pain during obstruction. In the present study, we examined whether (1) obstruction changes the expression of the two cyclooxygenase (COX) isoforms, COX-1 and COX-2 in human and rat ureters and (2) administration of a selective COX-2 inhibitor influences the pelvic pressure change after experimental ureteral obstruction. Rats were subjected to bilateral ureter obstruction. Ureters were removed and dissected into a proximal dilated and distal non-dilated segment. RNA and protein were extracted and analyzed for cyclooxygenase expression by quantitative polymerase chain reaction and Western blotting. Human ureter samples were obtained from patients undergoing radical nephrectomy. Rat and human ureteral samples were processed for immunohistochemistry. COX-1, but not COX-2 mRNA, was readily detected in the normal rat ureter. COX-2 mRNA and protein expression was increased in the proximal dilated ureter compared to distal non-dilated ureter. This increased COX-2 expression was associated with increased urinary prostaglandin E2 (PGE2) excretion after release of obstruction. Immunohistochemistry showed increased COX-2 labeling in surface epithelium and smooth muscle layers in both rat and human obstructed ureters compared to control ureters. Furthermore, contractile PGE2-EP1 and thromboxane TP receptors were expressed in ureteral smooth muscle. Systemic treatment with the COX-2 selective inhibitor parecoxib (5 mg/kg/day) attenuated the pelvic pressure increase during obstruction. In summary, COX-2 expression is significantly increased in the ureteral wall in response to obstruction in the rat and human ureter and COX-2 activity contributes to increased pelvic pressure after obstruction.
Nørregaard
R
R
The Water and Salt Research Center, University of Aarhus, Aarhus C, Denmark.
Jensen
B L
BL
Topcu
S O
SO
Nielsen
S S
SS
Walter
S
S
Djurhuus
J C
JC
Frøkiaer
J
J
D000818:Animals; D051545:Cyclooxygenase 1 / Q000235:genetics / Q000378:metabolism; D051546:Cyclooxygenase 2 / Q000378:metabolism*; D052246:Cyclooxygenase 2 Inhibitors; D015232:Dinoprostone / Q000235:genetics / Q000378:metabolism; D005786:Gene Expression Regulation / Q000502:physiology; D015971:Gene Expression Regulation, Enzymologic / Q000502:physiology; D006801:Humans; D007555:Isoxazoles; D008297:Male; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D010388:Pelvis / Q000503:physiopathology*; D011312:Pressure; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D011982:Receptors, Prostaglandin / Q000235:genetics / Q000378:metabolism; D014513:Ureter / Q000201:enzymology* / Q000473:pathology / Q000503:physiopathology; D014517:Ureteral Obstruction / Q000201:enzymology* / Q000503:physiopathology*
D052246:Cyclooxygenase 2 Inhibitors; D007555:Isoxazoles; D008565:Membrane Proteins; D012333:RNA, Messenger; D011982:Receptors, Prostaglandin; C409945:parecoxib; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; C496511:PTGS1 protein, human; C496513:Ptgs1 protein, rat; D015232:Dinoprostone