Human bladder smooth muscle cell damage in disturbed oxygen tension.

Objective: To characterize human bladder smooth muscle cell reactions to disturbed oxygen tension. Clinical studies have shown a close correlation between bladder ischemia and lower urinary tract symptoms in elderly patients.

Materials And Methods: Confluent cultured human bladder smooth muscle cells were incubated under normoxia, continuous hypoxia, and oxidative stress (hypoxia/reoxygenation) conditions using a computerized oxycycler system. After 48 hours, cell samples were collected and processed for fluorometric assessment of oxidative injury, enzyme immunoassay of antioxidant capacity, and transmission electron microscopy.

Results: Lipid peroxidation was found in cell hypoxia and oxidative stress, whereas protein oxidation was evident in oxidative stress only. Cell antioxidant capacity decreased in oxidative stress but remained unchanged in hypoxia. Oxidative products were present in cell oxidative stress only, whereas nitrosative products increased in both hypoxia and oxidative stress conditions. Forty-eight hours of hypoxia and oxidative stress had no effect on cell senescence. Thickened deformed cell membrane, swollen mitochondria, and enlarged endoplasmic reticulum (ER) were found in cell hypoxia. Partially lost cell membrane with increased caveolae, swollen mitochondria with degraded cristae, splintered ER, and increased lysosomes were evident in cell oxidative stress.

Conclusion: Human bladder smooth muscle cells are highly reactive to nonconforming oxygen tension. Reactions to hypoxia are consistent with cell survival signaling to cope with lack of oxygen. Changes in oxidative stress indicate extensive damage and deterioration of the subcellular elements. Hypoxic and oxidative damage may be an important mechanism of smooth muscle degeneration in bladder conditions with disturbed oxygen tension.