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Effects of fasudil, a Rho-kinase inhibitor, on contraction of pig bladder tissues with or without urothelium.

Authors :
Tatsumiya, Katsuhisa
Yamanishi, Tomonori
Watanabe, Miho
Masuda, Akinori
Mizuno, Tomoya
Kamai, Takao
Yoshida, Ken-Ichiro
Source :
International Journal of Urology; Dec2009, Vol. 16 Issue 12, p959-966, 8p, 1 Chart, 2 Graphs
Publication Year :
2009

Abstract

Objectives: To investigate the effects of fasudil, a Rho-associated serine-threonine protein kinase inhibitor, on contraction of the pig urinary bladder tissues with or without urothelium. Methods: Cumulative concentration-response curves (CRCs) to carbachol were obtained with and without 3–10 µM fasudil. Drug effects were evaluated in detrusor with and without urothelium. Inhibitory responses to fasudil were also examined in tissues precontracted with KCl and carbachol, and in response to electrical field stimulation, in pig bladder with and without urothelium. Results: In detrusor without urothelium, maximum contraction (E<subscript>max</subscript>) decreased after administration of fasudil at 3 or 10 µmol/L (both P < 0.01), or 30 µmol/L (72.5 ± 7.43%, 58.4 ± 8.04% and 68.4 ± 9.6%, respectively, of the first curve). In detrusor with urothelium, E<subscript>max</subscript> decreased significantly (all P < 0.05) after the addition of 3, 10 or 30 µmol/L of fasudil (84.9 ± 6.7%, 67.9 ± 5.2% and 35.2 ± 4.1%, respectively). In tissues precontracted with 80 mmol/L KCl or 100 µmol/L carbachol, tension after administration of fasudil (1 nmol/L to 100 µmol/L) decreased (by approximately 40%), only after administration of fasudil at high concentration (>1 µmol/L), in detrusor both with and without urothelium. In tissues with and without urothelium, responses to electrical field stimulation at 1–50 Hz decreased significantly in a concentration-dependent manner after addition of fasudil (3 to 30 µmol/L). Conclusions: Fasudil seems to provoke relaxation of the bladder detrusor via both urothelium-dependent and independent pathways. [ABSTRACT FROM AUTHOR]

Details

Language :
English
ISSN :
09198172
Volume :
16
Issue :
12
Database :
Complementary Index
Journal :
International Journal of Urology
Publication Type :
Academic Journal
Accession number :
45393814
Full Text :
https://doi.org/10.1111/j.1442-2042.2009.02397.x