Activation of the calcineurin pathway is associated with detrusor decompensation: a potential therapeutic target.
PURPOSE: We hypothesized that the calcineurin pathway mediated some of the complex remodeling process that allows a bladder subjected to partial outlet obstruction to adapt to its new workload. Atrial natriuretic factor mRNA expression served as a marker of calcineurin activation.
MATERIALS AND METHODS: A total of 16 New Zealand White rabbits underwent surgical creation of partial outlet obstruction, followed by randomization to receive cyclosporin A (20 mg/kg intramuscularly twice daily) or no additional treatment for 14 days. Three animals underwent 2 weeks of partial bladder outlet obstruction followed by bladder biopsy and the reversal of obstruction.
RESULTS: Atrial natriuretic factor expression was seen only in bladders with severe hypertrophy and it disappeared with the reversal of outlet obstruction. Cyclosporin A treatment resulted in a decrease in atrial natriuretic factor mRNA expression (p
CONCLUSIONS: The calcineurin pathway has a significant role in bladder wall hypertrophy following partial outlet obstruction. Bladder hypertrophy could not be fully prevented by cyclosporin A, suggesting that multiple signaling pathways are involved in this pathophysiology. The expression of myosin heavy chain AB isoforms is regulated in part by the calcineurin pathway.
Published In/Presented At
Clement, M. R., Delaney, D. P., Austin, J. C., Sliwoski, J., Hii, G. C., Canning, D. A., DiSanto, M. E., Chacko, S. K., & Zderic, S. A. (2006). Activation of the calcineurin pathway is associated with detrusor decompensation: a potential therapeutic target. The Journal of urology, 176(3), 1225–1229. https://doi.org/10.1016/j.juro.2006.04.027
Medicine and Health Sciences | Pediatrics
Department of Pediatrics