The Influence of Rho-Kinase Inhibition on Acetic Acid-Induced Detrusor Overactivity

Aims: Accumulating evidence has shown that Rho-kinase ( ROCK) is involved in the regulation of bladder contraction. Our objective was to examine whether the ROCK inhibitor, GSK 269962, could prevent acetic acid ( AA)-induced detrusor overactivity and to assess its influence on urine production ( UP) and mean arterial pressure ( MAP). Methods: The bladder was catheterized from the external urethral orifice. 0.25%( AA) solution was infused into the bladder for 5 min. In the same session a catheter was inserted into the apex of the bladder dome. In order to measure the blood pressure, the carotid artery was cannulated. Three days after the intravesical instillation of AA, the ROCK-GSK 269962 inhibitor was administered in a single dose of 10 mg/kg and a cystometry was carried out, along with a 24 hr measurement of UP and MAP. Results: GSK 269962 reversed the changes induced by AA causing a drop in basal pressure, threshold pressure, micturition voiding pressure, bladder contraction duration, relaxation time, detrusor overactivity index, amplitude, and frequency of nonvoiding contractions while an increase in voided volume, post-void residual, volume threshold, voiding efficiency, intercontraction interval, bladder compliance, and volume threshold to elicit nonvoiding contractions. ROCK inhibition did not show any significant changes in UP and MAP. Discussion: The results obtained indicate that ROCK inhibition may ameliorate AA-induced bladder overactivity. Conclusion: ROCK inhibitors appear to represent a potentially attractive pharmacological option for the treatment of lower urinary tract disorders associated with changes in detrusor contractility. (C) 2015 Wiley Periodicals, Inc.