Effects of varying degrees of partial bladder outlet obstruction on urinary bladder function of rats: A novel link to inflammation, oxidative stress and hypoxia

OBJECTIVES: The aim of the present study was to investigate the effects of different degrees of obstruction, and the roles of inflammation, oxidative stress, and hypoxia parameters on bladder function. METHODS: Thirty male Sprague-Dawley rats were divided into 3 groups (n = 10 in each group): (i) sham-operated control; (ii) severe partial bladder outlet obstruction (PBOO); and (iii) moderate PBOO. Severe and moderate PBOO were induced by urethral ligation using 3-Fr and 4-Fr catheters, respectively, for 6 weeks. After 6 weeks, the in vitro contractile responses to carbachol, electrical field stimulation, ATP and KCl were measured in bladder strips. In addition, mRNA and protein expression of nuclear factor kappa B (NF-κB) hypoxia-inducible factor (HIF) and nuclear factor, erythroid 2-like 2 (Nrf2) in bladder were determined by real-time polymerase chain reaction and western blotting. Malondialdehyde (MDA) levels in bladder tissues were also determined. RESULTS: Rats in the severe PBOO group had the highest bladder weight. Detrusor strips from rats in the severe PBOO group exhibited 61%-82% smaller contractile responses to all four stimuli than those from the sham-operated group. Activity of NF-κB as an inflammatory marker was increased in the severe PBOO group, whereas HIF-1α and HIF-2β protein levels were increased significantly in the moderate PBOO group. A master regulator of oxidative stress, Nrf2 expression was increased in all obstructed rats. MDA levels were higher in the severe PBOO group than in sham-operated group. CONCLUSION: The results of the present study reveal the importance of oxidative stress-induced NF-κB signaling in bladder dysfunction with severe obstruction. Altered HIF signaling may contribute to the functional impairment after PBOO. Novel and evolving therapies targeting oxidative and/or inflammatory pathways may be a reasonable strategy for the management of lower urinary tract symptoms or benign prostatic hyperplasia.