Effects of fasudil, a Rho-kinase inhibitor, on contraction of pig bladder tissues with or without urothelium.
OBJECTIVE
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 microM 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(max)) decreased after administration of fasudil at 3 or 10 micromol/L (both P < 0.01), or 30 micromol/L (72.5 + or - 7.43%, 58.4 + or - 8.04% and 68.4 + or - 9.6%, respectively, of the first curve). In detrusor with urothelium, E(max) decreased significantly (all P < 0.05) after the addition of 3, 10 or 30 micromol/L of fasudil (84.9 + or - 6.7%, 67.9 + or - 5.2% and 35.2 + or - 4.1%, respectively). In tissues precontracted with 80 mmol/L KCl or 100 micromol/L carbachol, tension after administration of fasudil (1 nmol/L to 100 micromol/L) decreased (by approximately 40%), only after administration of fasudil at high concentration (>1 micromol/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 micromol/L).


CONCLUSIONS
Fasudil seems to provoke relaxation of the bladder detrusor via both urothelium-dependent and independent pathways.
Tatsumiya
Katsuhisa
K
Department of Urology, Dokkyo Medical University, Mibu, Tochigi, Japan.
Yamanishi
Tomonori
T
Watanabe
Miho
M
Masuda
Akinori
A
Mizuno
Tomoya
T
Kamai
Takao
T
Yoshida
Ken-Ichiro
K
D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine / Q000031:analogs & derivatives* / Q000494:pharmacology; D000818:Animals; D002217:Carbachol / Q000494:pharmacology; D018679:Cholinergic Agonists / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004558:Electric Stimulation; D005260:Female; D066298:In Vitro Techniques; D009119:Muscle Contraction / Q000187:drug effects*; D009126:Muscle Relaxation / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects / Q000502:physiology; D011189:Potassium Chloride / Q000494:pharmacology; D047428:Protein Kinase Inhibitors / Q000494:pharmacology*; D013552:Swine; D001743:Urinary Bladder / Q000187:drug effects* / Q000502:physiology; D019459:Urothelium / Q000187:drug effects* / Q000502:physiology; D054460:rho-Associated Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism
D018679:Cholinergic Agonists; D047428:Protein Kinase Inhibitors; D011189:Potassium Chloride; D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D002217:Carbachol; D054460:rho-Associated Kinases; C049347:fasudil