The Effect of In Vitro Oxidative Stress on the Female Rabbit Bladder Contractile Response and Antioxidant Levels

Introduction. There are several bladder dysfunctions that are associated with oxidative stress to the urinary bladder. Two experimental models are known to cause this type of bladder damage. The first is direct oxidative damage caused by hydrogen peroxide (H2O2). The second is oxidative damage caused by ischemia followed by reperfusion (I/R). The specific aim of this study is to directly compare these two models of oxidative stress. Methods. Six adult female NZW rabbits were divided into two groups of three rabbits each. Eight full thickness strips from three rabbit bladders were taken for in vitro ischemia/reperfusion physiological analysis, while eight strips from three rabbit bladders were taken for in vitro H2O2 physiological analysis. All tissue was analyzed for total antioxidant activity (AA) and malondialdehyde (MDA) levels. In addition, samples of the water baths were also analyzed for AA. Results. In vitro I/R reduced the response to field stimulation (FS) to a significantly greater extent than the inhibition of the response to carbachol. In vitro H2O2 decreased all responses to approximately the same degree. Total AA levels at higher concentrations of H2O2 for all bath fluids were significantly higher than controls. MDA levels were significantly elevated in both models of oxidative stress. 1. Introduction There are several lower urinary tract dysfunctions (LUTD) that are more prevalent in women than men including interstitial cystitis, recurrent urinary tract infections, and incontinence [1, 2]. The bladder is composed of a thick smooth muscle wall. The inner most tissue layer of the bladder wall, the mucosa (urothelium), is intimately associated with lower urinary tract function [3]. The mucosa is the first line of defense against bladder infections and the penetration of urine solutes into the bladder tissue. The glycosaminoglycan coating of the mucosal surface presents a nonadherent surface to most strains of bacteria and an impermeable barrier to urinary solutes [4–7]. We believe that incontinence, recurrent urinary tract infections, and interstitial cystitis are related directly to estrogen levels. Low estrogen can induce a significant decrease in blood flow to the bladder especially in the mucosa resulting in free radical generation (oxidative stress) and a breakdown in mucosal integrity [8–10]. The etiology of these dysfunctions involves an increase in urothelial permeability and the movement of urinary solutes such as ions and other caustic substances from the urine into the mucosa, submucosa, and muscle. This results in both the