Effects of intravesical instillation of cyclooxygenase-2 inhibitor on the expression of inducible nitric oxide synthase and nerve growth factor in cyclophosphamide-induced overactive bladder.
OBJECTIVE
To examine the effects of intravesical cyclooxygenase-2 (COX-2) inhibitors on the expression of inducible nitric oxide synthase (iNOS) and nerve growth factor (NGF) in cyclophosphamide (CYP)-induced overactive bladder (OAB).


METHODS
In all, 40 Sprague-Dawley rats were divided into control, OAB, and COX-2 inhibitor-treated groups. OAB was induced by an intraperitoneal injection with CYP. Cystometry was performed in all rats and, in half of the OAB rats, a COX-2 inhibitor was administered intravesically. The bladders of all rats were stained immunohistochemically for iNOS and NGF.


RESULTS
In the OAB rats, the contraction interval and intercontraction interval were significantly shorter than in control rats, and the contraction time and pressure were significantly greater. In the COX-2 inhibitor-treated rats, the contraction interval and intercontraction interval were significantly longer than in the OAB rats, and the contraction time was significantly shorter. On immunohistochemical staining, there was no iNOS activity and NGF activity was minimally localized in the mucosa and submucosa in the control group. In the OAB rats, NGF activity in the mucosa and submucosa were increased, and there was greater expression of iNOS in all layers and of NGF in detrusor; in the COX-2 inhibitor-treated rats, their expression was less in all layers.


CONCLUSIONS
Intravesical instillation with COX-2 inhibitors can reduce CYP-induced bladder hyperactivity and expression of iNOS and NGF. Intravesical instillation with COX-2 inhibitors can be considered as a possible treatment for OAB.
Jang
Joon
J
Department of Urology, College of Medicine, The Catholic University, Seoul, Korea.
Park
Eun Young
EY
Seo
Seong Il
SI
Hwang
Tae-Kon
TK
Kim
Joon Chul
JC
D000818:Animals; D052246:Cyclooxygenase 2 Inhibitors / Q000627:therapeutic use*; D003520:Cyclophosphamide; D007150:Immunohistochemistry; D007783:Lactones / Q000627:therapeutic use*; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D020932:Nerve Growth Factor / Q000378:metabolism*; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism*; D009929:Organ Size; D051381:Rats; D017207:Rats, Sprague-Dawley; D013450:Sulfones / Q000627:therapeutic use*; D001743:Urinary Bladder / Q000473:pathology; D014549:Urinary Incontinence / Q000139:chemically induced / Q000188:drug therapy* / Q000201:enzymology
D052246:Cyclooxygenase 2 Inhibitors; D007783:Lactones; D013450:Sulfones; C116926:rofecoxib; D003520:Cyclophosphamide; D020932:Nerve Growth Factor; D052247:Nitric Oxide Synthase Type II