Enhanced Sensitivity to Afferent Stimulation and Impact of Overactive Bladder Therapies in the Conscious, Spontaneously Hypertensive Rat

Abstract

The spontaneously hypertensive rat (SHR) has been proposed as an overactive bladder model, driven, at least partially, by alterations in bladder innervation. To assess the functional role of sensory bladder afferents we evaluated the conscious cystometric response to prostaglandin E 2 (PGE 2 ) or acetic acid (AA) bladder infusion. SHR demonstrated a hypersensitivity to PGE 2 and AA, as indicated by a greater reduction in both void volume (VV) and micturition interval (MI) compared with Sprague-Dawley controls. The heightened PGE 2 and AA responses in the SHR were inhibited by capsaicin desensitization, supporting a role for bladder afferents in facilitating the hypersensitivity. Furthermore, we characterized the SHR pharmacologically using overactive bladder therapeutic agents. In the SHR, both darifenacin and oxybutynin (M 3 -selective and nonselective muscarinic antagonists, respectively) reduced micturition pressure (MP) and functional bladder capacity (VV and MI). In sharp contrast, functional bladder capacity was significantly enhanced by, and by gabapentin, without effect on MP. These data provide the first functional evidence for hypersensitive bladder afferents in the SHR and provide a pharmacological benchmark in this model for overactive bladder therapeutics. These data also support the idea that ␤ 3 -adrenoceptor agonism and gabapentin may provide a more effective overactive bladder therapy than muscarinic antagonism.

A Novel Mouse Model of Chronic Inflammatory and Overactive Bladder by a Single Intravesical Injection of Hydrogen Peroxide

“…Taken together, it is suggested that the long-lasting bladder hyperactivity is induced by prolonged inflammatory responses triggered by H 2 O 2 -mediated acute injury to the bladder. The inflammatory mediators such as inflammatory cytokines, chemokines, prostaglandins, and endogenous ROS, produced from infiltrated inflammatory cells could induce the hypersensitivity of the bladder sensory nerves, which can lead to the overactive bladder (30,39,40). The present findings are consistent with, at least in part, clinical features of IC patients.…”

Frequency analysis of urinary bladder pre-voiding activity in normal and overactive rat detrusor

“…Our results showed no significant difference in the maximum pressure before voiding in saline and acetic acid (Table ), in line with the findings of other investigators using the same model of detrusor overactivity (i.e., acetic acid inducing detrusor overactivity). The filled volume values also agreed with other studies reporting a significant reduction of bladder capacity when the bladder was filled with acetic acid . The rat model with acetic acid infusion, therefore, exhibited an increase in urinary frequency (i.e., voiding occurs at lower filled volumes), rather than non‐voiding activity as in the human overactive bladder.…”

Pathways Involving Beta‐3 Adrenergic Receptors Modulate Cold Stress‐Induced Detrusor Overactivity in Conscious Rats

“…In this study, we showed that CL316243 affected RT bladder functions by decreasing basal and micturition pressures and increasing voiding interval and bladder capacity. Also, similar urinary bladder effects were reported in rat disease models such as cerebral infarct and spontaneous hypertension . These results suggest that CL316243 might affect certain aspects of bladder functions.…”

“…This pattern was very similar to results in resiniferatoxin‐treated rats . While the mechanism of the beta‐3 AR agonist treatments are different from the resiniferatoxin treatments, a common feature of the two is the increase of urine storage. Thus, the partial reduction in the cold stress‐induced detrusor overactivity might be caused by the relaxation of the urinary detrusor promoted by CL316243.…”