Physiologic sequelae of partial infravesical obstruction in the mouse: Role of inducible nitric oxide synthase

Purpose: To develop a mouse model for partial infravesical obstruction, and determine the resultant changes in bladder function, with particular empha sis on the role of inducible nitric oxide synthase (iNOS) in the bladder re sponse. Materials and Methods: Wild type mice were subjected to no intervention, sh am operation, and varying durations of partial outlet obstruction (1, 3, an d 5 weeks). They then underwent cystometric evaluation, bladder strip stimu lation studies using carbachol, and relaxation studies using l-arginine, so dium nitroprusside, and 8-bromoguanosine 3'-5' cyclic guanosine monophospha te. Bladder tissue was subjected to RT-PCR and Western analysis for iNOS. B ladders were also studied histologically using morphometric analysis. Results: Bladders from mice obstructed for 5 weeks were heavier (weight inc reased by 110%), larger (capacity increased by 73%), and had a higher frequ ency of abnormal appearing cystometric curves than normal bladders. Tissue bath studies demonstrated decreased contractility in response to cholinergi c stimulation at 5 weeks of obstruction (decreased by 55% at maximal stimul ation). RT-PCR demonstrated iNOS in approximately 70% of bladders obstructe d for 1 and 3 weeks, while the iNOS protein was apparent in 50% of the blad ders from the same groups. Conclusions: This new animal model of infravesical obstruction is reliable and reproducible. Moreover, the physiologic changes noted are comparable to other models, but an added advantage is the relevance of this model with r egard to studying new transgenic or knockout mice. Enhanced expression of i NOS seen early after obstruction may serve to improve oxygenation during ob struction-induced ischemia.