AIMS: Reactive nitrogen and oxygen species (RNOS) likely play a role in the development of bladder dysfunction related to bladder outlet obstruction. Antioxidants protect against these free radicals. The aim of our study was to investigate the effect of bladder outlet obstruction on the endogenous antioxidant status of the bladder and to correlate this to bladder structure and function. METHODS: In 16 guinea pigs either a partial outlet obstruction or a sham operation was induced. The contractile responses of detrusor strips to electrical field stimulation (EFS), acetylcholine, potassium, and ATP were monitored 4 weeks after the operation. The nerve density in bladder tissue was determined by using the non-specific nerve marker PGP 9.5. Separate antioxidants and the total antioxidant status were assessed using the trolox equivalent antioxidant capacity (TEAC) test. RESULTS: Contractile responses of detrusor strips to EFS were for the greater part based on neurogenic stimulation. The nerve-mediated responses in strips from obstructed bladders were lower compared to the sham group. Obstructed bladders showed a patchy denervation and the nerve density was significantly lower compared to the sham group. The total antioxidant capacity, the glutathione and the glutathione reductase (GR) levels significantly decreased in obstructed bladders compared to the sham group. CONCLUSION: This study demonstrates that the antioxidant status of guinea pig bladders exposed to outlet obstruction decreased which might be associated with the observed reduction in nerve density. The results strengthen the hypothesis that oxidative stress is involved in the pathophysiology of bladder dysfunction related to obstructed bladders. Neurourol. Urodynam. (c) 2008 Wiley-Liss, Inc.