Dissimilar Effects of Tolterodine on Detrusor Overactivity in Awake Rats with Chemical Cystitis and Partial Bladder Outlet Obstruction

Abstract

PurposeWe investigated bladder function, with a special focus on nonvoiding contractions (NVCs), in awake rats with chronic chemical cystitis and bladder outlet obstruction (BOO) by use of simultaneous registrations of intravesical and intraabdominal pressures. In addition, we tested the effects of tolterodine on the NVCs in these models.MethodsA total of 20 female Sprague-Dawley rats were used in this study. In eight rats, chemical cystitis was induced by intravesical instillation of HCl. Twelve rats were subjected to sham instillations or partial BOO. Four weeks after intravesical instillation or 2 weeks after partial BOO, cystometrograms were obtained by use of simultaneous recording of intravesical and intraabdominal pressure in all unanesthetized, unrestrained rats in metabolic cages.ResultsA total of 17 rats survived. In the rats with acute injury by HCl, 50% showed detrusor overactivity (DO), which was not seen in the sham group. The cystitis group had lower DO pressure without a difference in DO frequency compared with the BOO group. After the administration of tolterodine, the cystitis group showed no difference in DO frequency or pressure, whereas the BOO group showed decreased values for both parameters.ConclusionsOur study showed that toleterodine produced no effect on DO during the filling phase in rats with chronic chemical cystitisbut decreased the frequency and pressure of DO in rats with BOO. Clinically, studies are needed to improve the treatment effect of anticholinergic drugs ininterstitial cystitis patients with overactive bladder.

Synergic Suppressive Effect of Silodosin and Imidafenacin on Non‐Voiding Bladder Contractions in Male Rats with Subacute Bladder Outlet Obstruction

“…These results suggest that the highest dose (10 µg/kg) of imidafenacin used was high enough to impair voiding function, whereas the intermediate dose (3 µg/kg) suppressed the NVCs without affecting the voiding function. These results are consistent with the previous studies that toleterodine, a non‐selective antimuscarinic agent, decreased the frequency and pressure of NVCs in rats with BOO . Regarding the action site of imidafenacin, the results of previous studies implicate that imidafenacin does not cross the blood–brain barrier easily and thus suggest that this drug most probably acts on the bladder muscarinic receptors …”

Flow Starting Point and Voiding Mechanisms Measured by Simultaneous Registrations of Intravesical, Intra-abdominal, and Intraurethral Pressures in Awake Rats

“…Based on the fact that, without the IPHFOs, the bladder contains significant amounts of residual urine [10,19,25,26], IPHFOs are presumed to be responsible for efficient voiding in male [6,25] and female [7] rats. However, their exact role in voiding remains controversial.…”

Effects of ritobegron (KUC-7483), a novel β₃-adrenoceptor agonist, on both rat bladder function following partial bladder outlet obstruction and on rat salivary secretion: a comparison with the effects of tolterodine

“…Indeed, only at a dose of 3 mg/kg did it decrease the amplitude of NVC. In previous studies, tolterodine significantly decreased both the frequency and amplitude of NVC (Jin et al, 2011). The explanation for this discrepancy is unclear, but it may be related to the experimental conditions (i.e., drug administration route and/or duration of partial BOO).…”