Ovariectomy May Induce Detrusor Overactivity in Rats: The Therapeutic Role of Rho Kinase Inhibition

Abstract

To verify the impact of ovariectomy (OVX) on the micturition cycle in conscious rats; to examine the influence of rho kinase (ROCK) inhibition on the bladder detrusor in OVX rats; to assess the effect of the joint administration of the ROCK inhibitor (GSK 269962) and solifenacin succinate (SOL) to these animals. The impact of OVX or a single dose of GSK 269962 and/or SOL on the cystometric parameters was assessed 28 days after the procedure. OVX caused an increase in detrusor overactivity index, amplitude, and frequency of nonvoiding contractions, along with a decrease in voided volume, volume threshold, intercontraction interval, bladder compliance, and volume threshold to elicit nonvoiding contractions. GSK 269962 administered in a dose of 10 mg/kg (but not 5 mg/kg) or SOL in a dose of 0.03 mg/kg (but not 0.015 mg/kg) triggered an increase in voided volume, volume threshold, intercontraction interval, bladder compliance, and volume threshold to elicit nonvoiding contractions, along with a decrease in detrusor overactivity index, amplitude, and frequency of nonvoiding contractions. A combined administration of GSK 269962 (5 mg/kg) and SOL (0.15 mg/kg), in doses ineffective in monotherapy, triggered a reversal in the OVX-induced cystometric changes. It appears that ROCK inhibitors can become an alternative worth considering in overactive bladder syndrome treatment, especially in the light of the findings pointing to the decreased efficiency of antimuscarinic drugs in the overactive bladder syndrome treatment of postmenopausal women.