Dysfunctional voiding behavior and impaired muscle contractility in a rat model of detrusor underactivity. Issue 8 (28th August 2021)

• Record Type: Journal Article
• Authors: Gonzalez, Eric J.; Odom, Michael R.; Hannan, Johanna L.; Grill, Warren M.
• Is Part Of: Neurourology and urodynamics. Volume 40:Issue 8(2021)
• Page Start: 1889
• Page End: 1899
• Publication Date: 2021-08-28
• Subjects: detrusor underactivity -- myography -- urethra -- urodynamics; Urinary organs -- Periodicals; Urodynamics -- Periodicals; Urology -- Periodicals; 616.6
• DOI: 10.1002/nau.24777
• Languages: English
• ISSNs: 0733-2467

Abstract

Abstract: Aims: Detrusor underactivity (DU) is an understudied health concern with inadequate clinical management. The pathophysiology of DU is unclear, and current therapies fail to improve symptoms. The current studies characterized voiding function and contractility of bladder and urethral tissues in a novel rat model of DU. Methods: Female obese prone (OP) and obese resistant (OR) rats were fed a 60 kcal% fat diet at 8 weeks old. A subset of rats ( n = 4/strain) underwent uroflowmetry biweekly for 18 weeks in metabolic cages. At 40–56 weeks old, rats ( n = 9–10/strain) underwent instrumented cystometry under urethane anesthesia. Following cystometry, bladder and urethral tissues ( n = 8–9/strain) were harvested for in vitro assessments of contractility in response to carbachol, electric field stimulation, atropine, alpha, beta‐methylene ATP, and caffeine. Results: OP rats exhibited increased urinary frequency ( p = 0.0031), decreased voided volume ( p = 0.0093), and urine flow rate ( p = 0.0064) compared to OR rats during uroflowmetry. Bethanechol (10 mg/kg) did not alter uroflowmetry parameters. During cystometry, OP rats exhibited decreased bladder emptying efficiency ( p < 0.0001), decreased pressure to generate a void ( p < 0.0001), and increased EUS activity during filling ( p = 0.0011). Bladder contractility was decreased in OP rats when exposed to carbachol ( p < 0.0003) and ATP ( p = 0.0004), whereas middle urethral contractility was increased when exposed to carbachol ( p = 0.0014), EFS ( p = 0.0289), and caffeine ( p = 0.0031). Conclusion: Impaired cholinergic and purinergic signaling in the bladder may contribute to poor voiding function in OP rats. In addition, increased urethral activity may engage a guarding reflex to augment continence and exacerbate incomplete emptying.