Karl-Erik Andersson led the peer-review process as the Associate Editor responsible for the paper.
Dual involvements of cyclooxygenase and nitric oxide synthase expressions in ketamine-induced ulcerative cystitis in rat bladder
Article first published online: 28 JAN 2013
© 2013 Wiley Periodicals, Inc.
Neurourology and Urodynamics
Volume 32, Issue 8, pages 1137–1143, November 2013
How to Cite
Chuang, S.-M., Liu, K.-M., Li, Y.-L., Jang, M.-Y., Lee, H.-H., Wu, W.-J., Chang, W.-C., Levin, R. M. and Juan, Y.-S. (2013), Dual involvements of cyclooxygenase and nitric oxide synthase expressions in ketamine-induced ulcerative cystitis in rat bladder. Neurourol. Urodyn., 32: 1137–1143. doi: 10.1002/nau.22367
Shu-Mien Chuang and Keh-Min Liu contributed equally to this manuscript.
Conflict of interest: none.
- Issue published online: 24 OCT 2013
- Article first published online: 28 JAN 2013
- Manuscript Accepted: 11 DEC 2012
- Manuscript Received: 4 SEP 2012
- Department of Medical Research, Kaohsiung Medical University Hospital. Grant Number: KMUH-100-0R44
- Kaohsiung Medical University. Grant Number: KMU-Q098015
- Kaohsiung Municipal Hsiao-Kang Hospital. Grant Number: KNHK-100-025
- nitric oxide synthase;
- ulcerative cystitis
The aims of the present study were to investigate voiding patterns, tissue constituents and the expressions of cyclooxygenase-2 (COX-2) and nitric oxide synthase (NOS) involved in ketamine-induced ulcerative cystitis in rat urinary bladder.
Thirty Sprague–Dawley rats were distributed into three groups which received saline or ketamine (25 mg/kg/day) for a period of 14 and 28 days. In each group, cystometry was performed weekly and the concentration of ketamine and its metabolites (norketamine) was assayed. Paraffin-embedded sections were stained with Masson's trichrome stain, and ketamine-induced morphological changes were examined. Western blot analyses were carried out to examine the expressions of COX-2 and different NOS isoforms in bladder tissues. Immunofluorescence study was done to evaluate the expressions of COX-2 and macrophage infiltration (stained with ED-1 macrophage cell surface antigen) within the bladder.
Ketamine treatment resulted in bladder hyperactivity and the non-voiding contractions were significantly increased. The urine concentrations of ketamine and norketamine were much higher in ketamine-treated group. Moreover, ulcerated urothelium and mononuclear cell infiltration were noted in ketamine-treated group. These alterations in urodynamic functions and tissue constituents were accompanied by increases in the expression of COX-2. Two NOS isoforms (iNOS and eNOS) were also overexpressed, but no significant change was observed for nNOS. COX-2 positive stained cells were significantly increased. Meanwhile, increased amounts of ED-1 positive stained macrophages were present and most of COX-2 expressed cells were co-stained with ED-1 in the early stage of ketamine treatment.
Ketamine treatment affected bladder tissues by enhancing interstitial fibrosis and accelerating macrophages infiltration. Ketamine also initiated the up-regulations of COX-2 and iNOS and eNOS expressions. These up-regulated enzymes might play an important role in contributing to ketamine-induced alterations in micturition patterns and ulcerative cystitis. Neurourol. Urodynam. 32:1137–1143, 2013. © 2013 Wiley Periodicals, Inc.