Effect of estrogen and ovariectomy on response of the female rabbit urinary bladder to two forms of in vitro oxidative stress

There are several lower urinary tract dysfunctions (LUTD) that are more common in women than in men including incontinence, interstitial cystitis, and recurrent urinary tract infection. There is increasing evidence that these dysfunctions are associated with reduced blood flow, ischemia, hypoxia, and reperfusion resulting in free radical generation and oxidative damage. The goal of the current study was to determine if the level of circulating estrogen affects the response of the bladder muscle and mucosa to two in vitro models of oxidative stress: Incubation in the presence of hydrogen peroxide (H2O2) is the first model; the second is ischemia followed by reperfusion which results in the direct production of damaging free radicals. The motivation for this study is the current literature linking female-related LUTD with oxidative stress. Eighteen female New Zealand white rabbits were divided into three groups: control, ovariectomized, and ovariectomized receiving continuous estrogen. Eight bladder strips from each of three rabbits per group were taken for in vitro ischemia/reperfusion (I/R) physiological experiments, while eight strips from the three remaining rabbit bladders per group were taken for in vitro H2O2 experiments. All tissue was analyzed for total antioxidant activity (AA) and malondialdehyde (MDA) levels. In addition, the organ bath buffer was also analyzed for AA. In vitro H2O2 was found to target the nerve, muscarinic receptor, and membrane equally causing more damage to bladder tissue than in vitro I/R. Ovariectomy resulted in lower contractility and higher lipid peroxidation. However, estrogen supplementation following ovariectomy protected the bladder against both models of oxidative stress by maintaining contractile responses to stimulation and decreasing lipid peroxidation. The primary conclusion from this study is high estrogen protects the bladder from oxidative stress, whereas low estrogen makes the bladder more susceptible.