Alteration in Contractile Responses in Human Detrusor Smooth Muscle from Obstructed Bladders with Overactivity

Abstract

Introduction: In this study, we aimed to evaluate changes in contractile responses under in vitro conditions in detrusor overactivity (DO) in patients with bladder outflow obstruction (BOO). Materials and Methods: Detrusor strips obtained during open prostatectomy procedure from 16 patients with BOO related to benign prostate hyperplasia were evaluated under in vitro conditions. Patients were assigned to two groups as patients with (DO) and without (no DO) DO. Four detrusor strips were prepared from each bladder in dimensions of 2 × 10 mm, and were suspended in organ bath. Responses to carbachol (10^–8 to 10^–3M), electrical field stimulation (EFS) (0.5–32 Hz), single-dose adenosine 5′-triphosphate (ATP) (10^–3M) and KCl (120 mM) were recorded to evaluate the contractile responses. EFS responses were repeated in the presence of NG-nitro-L-arginine methyl ester (L-NAME; 10 µM) and L-NAME + indomethacin. All responses were expressed as mg tension developed per mg of bladder tissue. Data obtained were compared using independent t test and one-way ANOVA test. Values of p < 0.05 were accepted as statistically significant. Results: Of the 16 patients on whom open prostatectomy was performed because of BOO, 8 of the patients were determined as no DO and 8 as DO. There were no differences between groups regarding age and residual urine. We found statistically significant differences between groups regarding dimensions of prostate, maximum bladder capacity and maximum bladder pressure. In the comparison of cumulative dose of carbachol, it was seen that responses were higher in the DO group, but the differences were not statistically significant. In EFS application, contractile responses were found to increase significantly in the DO group. No changes were observed between groups for ATP and KCl. EFS responses were found to be significantly higher in presence of L-NAME + indomethacin in the no DO group; however, no difference was seen in the DO group. Conclusions: Detrusor contractile responses to EFS increased in patients with BOO in presence of overactivity. These changes in contractile responses are observed possibly as a result of deterioration in neuromodulation, rather than as a result of changes in purinergic or cholinergic receptor sensation or level. We suggest that a noncholinergic-nonpurinergic mechanism can have some effect on these changes.

Impairment of ATP hydrolysis decreases adenosine A1 receptor tonus favoring cholinergic nerve hyperactivity in the obstructed human urinary bladder

“…Therefore, we hypothesized that deficits in adenosine formation from released adenine nucleotides along with lifetime increments of ATP could contribute to detrusor overactivity in BPH patients. Deterioration of bladder neuromodulatory control has been hypothesized to explain the increase on nerveevoked detrusor contractions in obstructed patients [44]. We show here that detrusor strips from BPH patients release higher amounts of ATP and ACh when stimulated electrically.…”

Electrical propagation in the renal pelvis, ureter and bladder

“…, Kosan et al . ), there is no significant data on the alterations in the electrical propagation in these conditions. Bladder outflow obstruction and neurogenic bladder are two of the mostly investigated conditions.…”

Detrusor underactivity and the underactive bladder: Symptoms, function, cause-what do we mean? ICI-RS think tank 2014

“…This could be as a result of insufficient postganglionic efferent nerve stimulation e.g., poor central motor drive, such as in some brain injury (ischemia, trauma) patients, or due to neuropathic changes within the detrusor such as has been reported with aging and chronic outlet obstruction . While voiding detrusor contraction in humans is classically regarded as cholinergically mediated, other signalling pathways, primarily purinergic, may assume importance in disease and aging . While often associated with pathologic function, especially in aging, these changes may be adaptive, and failure of adaptive neuropharmacologic processes could impair the voiding contraction.…”