Systemic Atherosclerosis Causes Detrusor Overactivity: Functional and Morphological Changes in Hyperlipoproteinemic apoE-/- LDLR-/- Mice

Purpose: The prevalence of systemic atherosclerosis and overactive bladder/detrusor overactivity increases almost simultaneously with age but an association between these diseases has not yet been proved. We evaluated changes in bladder function and morphology, including vascularization, in apoE(-/-) LDLR-/- double knockout mice with systemic atherosclerosis but without central nervous system involvement. Materials and Methods: Cystometry was performed in awake, freely moving 60-week-old apoE(-/-) LDLR-/- mice and C57BL/6N controls. The mice were sacrificed and perfused with Microfil (R) contrast medium. The bladder was excised, dissected and scanned by nano-computerized tomography, including 3-dimensional reconstruction. Samples then underwent histomorphological analysis. Results: In apoE(-/-) LDLR-/- mice cystometry revealed a significant decrease in the peak-peak interval, micturition interval, functional bladder capacity and micturition volume. However, maximum bladder pressure increased. Nano-computerized tomography revealed a significant reduction in bladder wall thickness, segment volume, vascular volume and the vascular volume fraction. Histomorphologically bladder specimens showed a thickened media of intramural vessels, activated endothelial cells and intramural inflammatory cells. Conclusions: To our knowledge this study presents a new in vivo mouse model of nonneurogenic detrusor overactivity caused by systemic atherosclerosis. Decreased bladder wall vascularization seems to be a major factor for detrusor overactivity onset. Capillaries are rarified with reduced lumina due to thickened media. Activated endothelial cells and the infiltration of inflammatory cells in apoE(-/-) LDLR-/- mice underlines once more that atherosclerosis is an inflammatory process that may also be relevant to the onset of detrusor overactivity.