Effects of Ischemia and Oxidative Stress on Bladder Purinoceptors Expression

ObjectiveTo study the effects of chronic ischemia on bladder purinoceptors. A close correlation between bladder ischemia and lower urinary tract symptoms has been reported. Purinoceptors contribute to important aspects of bladder function including sensation, neural signaling, and voiding contraction. Our goal was to examine purinoceptors expression in the ischemic overactive bladder.Materials and MethodsModerate bladder ischemia was produced in rabbits by creating bilateral iliac artery atherosclerosis. After 8 weeks, bladder blood flow was measured, and cystometrograms were obtained. Bladder tissues from 8-week ischemic and age-matched control bladders were processed for the analysis of oxidative stress markers, P2X and P2Y purinoceptors expression, and transmission electron microscopy.ResultsArterial atherosclerosis significantly decreased bladder blood flow. Markers of oxidative stress characterized by increased levels of advanced oxidation protein products and malondialdehyde were evident in the ischemic bladder tissues. Chronic ischemia and oxidative stress decreased the bladder capacity and increased spontaneous bladder contractions. Bladder pressure at micturition and intravesical pressure rise during contractions tended to be greater in the ischemic bladder but did not reach significance. Transmission electron microscopy showed smooth muscle cell and microvasculature structural damage and diffuse fibrosis. These changes in the ischemic bladder were associated with significant increases in purinoceptors P2X1, P2X2, P2X3, P2X4, P2X5, and P2X7 expression. The P2Y isoforms were not expressed in the rabbit bladder.ConclusionStructural and functional changes in the chronically ischemic bladder were associated with upregulation of P2X receptor isoforms. Increased P2X expression may play a role in ischemia-induced bladder overactivity and noncompliance.