Activation of the Calcineurin Pathway is Associated With Detrusor Decompensation: A Potential Therapeutic Target

Michele R. Clement, Daniel P. Delaney, J. Christopher Austin, Joanna Sliwoski, George C. Hii, Douglas A. Canning, Michael E. DiSanto, Samuel K. Chacko, Stephen A. Zderic

Research output: Contribution to journalArticlepeer-review

14 Scopus citations

Abstract

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 <0.05) and a marked shift in myosin heavy chain A-to-B ratios toward normal (p <0.01) and an increase in smooth muscle cross sectional area (p <0.05). Bladder mass decreased 40% but did not attain statistical significance (p = 0.08). 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.

Original languageEnglish (US)
Pages (from-to)1225-1229
Number of pages5
JournalJournal of Urology
Volume176
Issue number3
DOIs
StatePublished - Sep 2006
Externally publishedYes

Keywords

  • bladder
  • bladder outlet obstruction
  • calcineurin
  • cyclosporine
  • muscle
  • smooth

ASJC Scopus subject areas

  • Urology

Fingerprint Dive into the research topics of 'Activation of the Calcineurin Pathway is Associated With Detrusor Decompensation: A Potential Therapeutic Target'. Together they form a unique fingerprint.

Cite this