Water avoidance stress induces frequency through cyclooxygenase-2 expression: a bladder rat model.

Abstract

OBJECTIVES:

Water avoidance stress is a potent psychological stressor and it is associated with visceral hyperalgesia, which shows degeneration of the urothelial layer mimicking interstitial cystitis. Cyclooxygenase-2 inhibitors have been recognized to ameliorate frequency both in clinical and experimental settings. We investigated the voiding pattern and cyclooxygenase-2 expression in a rat bladder model of water avoidance stress.

METHODS:

After being subjected to water avoidance stress or a sham procedure, rats underwent metabolic cage analysis and cystometrography. Real time reverse transcription polymerase chain reaction was carried out to examine cyclooxygenase-2 messenger ribonucleic acid in bladders of rats. Protein expression of cyclooxygenase-2 was analyzed with immunohistochemistry and western blotting. Furthermore, the effects of the cyclooxygenase-2 inhibitor, etodolac, were investigated by carrying out cystometrography, immunohistochemistry and western blotting.

RESULTS:

Metabolic cage analysis and cystometrography showed significantly shorter intervals and less volume of voiding in water avoidance stress rats. Significantly higher expression of cyclooxygenase-2 messenger ribonucleic acid was verified by reverse transcription polymerase chain reaction. Immunohistochemistry and western blotting showed significantly higher cyclooxygenase-2 protein levels in water avoidance stress bladders. Furthermore, immunohistochemistry showed high cyclooxygenase-2 expression exclusively in smooth muscle cells. All water avoidance stress-induced changes were reduced by cyclooxygenase-2 inhibitor pretreatment.

CONCLUSIONS:

Chronic stress might cause frequency through cyclooxygenase-2 gene upregulation in bladder smooth muscle cells. Further study of cyclooxygenase-2 in the water avoidance stress bladder might provide novel therapeutic modalities for interstitial cystitis.

• Authors: Keisuke Yamamoto, Tetsuya Takao, Jiro Nakayama, Hiroshi Kiuchi, Hidenobu Okuda, Shinichiro Fukuhara, Iwao Yoshioka, Yasuhiro Matsuoka, Yasushi Miyagawa, Akira Tsujimura, Norio Nonomura
• Journal: International journal of urology : official journal of the Japanese Urological Association (Int J Urol) Vol. 19 Issue 2 Pg. 155-62 (Feb 2012) ISSN: 1442-2042 [Electronic] Australia
• PMID: 22142485 (Publication Type: Comparative Study, Journal Article)
• Copyright: © 2011 The Japanese Urological Association.

Chemical References

• RNA
• Cyclooxygenase 2

Topics

• Animals
• Cyclooxygenase 2 (biosynthesis, genetics)
• Cystitis, Interstitial (complications, enzymology, genetics)
• Dehydration (enzymology, etiology, genetics)
• Disease Models, Animal
• Gene Expression Regulation
• Immunohistochemistry
• Male
• RNA (genetics)
• Rats
• Rats, Sprague-Dawley
• Real-Time Polymerase Chain Reaction
• Urinary Bladder (enzymology)