Inducible nitric oxide synthase promotes pathophysiological consequences of experimental bladder outlet obstruction.
OBJECTIVE
Bladder outlet obstruction leads to histological and functional changes in the bladder over time. We investigated the role of inducible nitric oxide synthase (iNOS) in the progression of pathological changes of the bladder secondary to outlet obstruction in a rat and a mouse model.


METHODS
To assess expression of iNOS in the bladder, polymerase chain reaction amplification of mRNA was done. Rats were subjected to sham operation or partial bladder outlet obstruction. They were given the iNOS inhibitor aminoguanidine in drinking water or unmodified water. After 2 weeks, awake cystometric evaluation was performed, the bladders were harvested and the degree of fibrosis was assessed. In another series of experiments mice deficient in the iNOS gene (iNOS -/-) were compared to WT mice for cystometric as well as histological changes in the bladder following partial bladder outlet obstruction or sham operation.


RESULTS
Partial bladder outlet obstruction induced the expression of iNOS mRNA in the mouse bladder. iNOS -/- mice showed a significantly smaller increase in bladder volume at 3 weeks compared with WT. Pharmacological inhibition of iNOS activity significantly attenuated the increase in bladder size and the number of spontaneous bladder contractions in obstructed rats at 2 weeks. Furthermore, genetic and pharmacological decreases in iNOS led to significantly less fibrosis of the bladder after partial bladder outlet obstruction in mice and rats, respectively.


CONCLUSIONS
Pharmacological or genetic decreases in iNOS resulted in amelioration of functional and fibrotic changes in the bladder after partial bladder outlet obstruction, suggesting that NO contributes to the pathophysiology of bladder outlet obstruction.
Felsen
Diane
D
Center for Pediatric Urology, Department of Urology, Children's Hospital of New York-Weill Medical College of Cornell University, New York, New York, USA.
Dardashti
Kambiz
K
Ostad
Michael
M
Lemer
Matthew L
ML
Gross
Steven S
SS
Chen
Jie
J
Vaughan
E D
ED
Poppas
Dix P
DP
D000818:Animals; D004790:Enzyme Induction; D005260:Female; D051379:Mice; D008810:Mice, Inbred C57BL; D019001:Nitric Oxide Synthase / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D001743:Urinary Bladder / Q000473:pathology / Q000503:physiopathology; D001748:Urinary Bladder Neck Obstruction / Q000473:pathology / Q000503:physiopathology*; D014563:Urodynamics / Q000502:physiology
D019001:Nitric Oxide Synthase