Effects of the Rho kinase inhibitor, hydroxyfasudil, on bladder dysfunction and inflammation in rats with HCl-induced cystitis.

Abstract

OBJECTIVE:

To evaluate the effect of the Rho kinase inhibitor, hydroxyfasudil, on bladder function in a rat model of HCl-induced chemical cystitis, and to elucidate the possible mechanisms associated with its therapeutic effect.

METHODS:

Female Sprague-Dawley rats with HCl-induced cystitis were given hydroxyfasudil (10 mg/kg, i.p.) for 7 days. Treatment efficacy was determined by comparing bladder function and histopathology to sham and untreated control rats. Bladder function was determined by cystometric analysis. Rho kinase activity was determined by quantitative reverse transcription polymerase chain reaction and signal inhibition of downstream Ras homolog member A/Rho kinase signaling molecules by western blot and immunohistochemistry.

RESULTS:

Treatment with hydroxyfasudil significantly improved bladder intercontraction intervals. Rats treated with hydroxyfasudil also showed a significant reduction of histopathological features associated with cystitis. Western blot and immunohistochemistry findings showed that hydroxyfasudil inhibited downstream molecules of Rho kinase that ameliorated changes associated with HCl-induced chemical cystitis, such as inflammatory cell recruitment and smooth muscle cell proliferation.

CONCLUSION:

The findings from the present study suggest a promising therapeutic role for hydroxyfasudil in bladder inflammation associated with cystitis.

• Authors: Nobutaka Shimizu, Marco A De Velasco, Tohru Umekawa, Hirotsugu Uemura, Kazuhiro Yoshikawa
• Journal: International journal of urology : official journal of the Japanese Urological Association (Int J Urol) Vol. 20 Issue 11 Pg. 1136-43 (Nov 2013) ISSN: 1442-2042 [Electronic] Australia
• PMID: 23419011 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2013 The Japanese Urological Association.

Chemical References

• hydroxyfasudil
• 1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine
• rho-Associated Kinases
• rhoA GTP-Binding Protein
• Hydrochloric Acid

Topics

• 1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine (analogs & derivatives, pharmacology, therapeutic use)
• Animals
• Cystitis, Interstitial (chemically induced, drug therapy, metabolism, pathology)
• Drug Evaluation, Preclinical
• Female
• Hydrochloric Acid
• Rats
• Rats, Sprague-Dawley
• Urinary Bladder (drug effects, metabolism, pathology)
• rho-Associated Kinases (antagonists & inhibitors, metabolism)
• rhoA GTP-Binding Protein (metabolism)