Inhibition of Contractility of Isolated Caprine Detrusor by the Rho Kinase Inhibitor Fasudil and Reversal by the Guanylyl Cyclase Inhibitor ODQ

Background

Rho kinase (also called rho-associated protein kinase or ROCK), a serine/threonine kinase, is involved in muscle contractility since it phosphorylates myosin light chain phosphatase, hence inhibiting it. This leads to enhanced muscle contractility. Fasudil is an inhibitor of rho kinase that has been approved for the treatment of cerebral vasospasm in some Asian countries.

Objective

In this study, we tested the ability of fasudil to inhibit the contractility of the isolated caprine (goat) detrusor.

Methods

Twelve caprine detrusor strips were contracted using 80 mM KCl before and after the administration of 3 concentrations (10, 30, and 60 µM) of fasudil. Two reversal agents, the guanylyl cyclase inhibitor ODQ (10 µm) and the P2X receptor agonist diadenosine pentaphosphate (DAPP) (10 µM), were tested for their ability to reverse the inhibitory effect of fasudil on isolated detrusor contractility.

Results

Fasudil caused a dose-dependent inhibitory effect of KCl-induced detrusor contractility that was statistically significant at 30 and 60 µM concentrations. The inhibitory effect of 30 µM fasudil on detrusor contractility was significantly reversed by the addition of ODQ, but not by the addition of DAPP.

Conclusions

These results suggest that fasudil inhibits the contractility of the isolated detrusor. Fasudil could be investigated for use in clinical conditions such as overactive bladder that require detrusor muscle relaxation.