Back to Search
Start Over
Urethral dysfunction and therapeutic effects of a PDE 5 inhibitor (tadalafil) in a rat model of detrusor underactivity induced by pelvic nerve crush injury
- Source :
- Neurourology and Urodynamics. 39:916-925
- Publication Year :
- 2020
- Publisher :
- Wiley, 2020.
-
Abstract
- Aims The urethral dysfunction produced by a rat model of peripheral neurogenic detrusor underactivity (DU) using pelvic nerve crush (PNC) injury was characterized and then tested with the administration of tadalafil, a phosphodiesterase type 5 (PDE 5) inhibitor. Methods Ten days after producing PNC rats, awake cystometrograms (CMGs) and isovolumetric cystometrograms with urethral perfusion pressure (IC-UPP) measurements were performed. Also, in control rats, IC-UPP was recorded before and after intravenous atropine administration to determine if the reduction of bladder contraction pressure affects urethral relaxation during voiding. Then, CMG and IC-UPP measurements in PNC rats were recorded after intravenous administration of tadalafil. Lastly, real-time polymerase chain reaction was used to measure transcript levels of neuronal nitric oxide synthases (nNOS), endothelial nitric oxide synthases, and PDE 5 in urethral specimens from PNC and control rats. Results PNC rats demonstrated the characteristics of DU in CMG. Also, PNC rats exhibited significant decreases in isovolumetric bladder contraction amplitudes and urethral relaxation. Atropine attenuated the amplitude of isovolumetric bladder contractions; however, atropine did not affect urethral relaxation in control rats. Tadalafil decreased postvoid residual and increased voiding efficiency without changing bladder contraction amplitude in PNC rats. Also, tadalafil improved the amplitude of urethral relaxation during bladder contraction in PNC rats. Urethral nNOS transcript levels were upregulated in PNC rats compared to control rats. Conclusions PNC rats revealed both DU and impaired urethral relaxation. PDE 5 inhibition in PNC rats enhanced urethral relaxation during voiding, resulting in improved voiding efficiency. Thus, urethral dysfunction could be a potential target for the treatment of inefficient voiding associated with neurogenic DU.
- Subjects :
- medicine.medical_specialty
Nitric Oxide Synthase Type III
Urology
Urinary Bladder
030232 urology & nephrology
Urination
Nitric Oxide Synthase Type I
Pelvis
Tadalafil
Rats, Sprague-Dawley
Crush Injuries
03 medical and health sciences
0302 clinical medicine
Urethra
Peripheral Nerve Injuries
Urinary Bladder, Underactive
medicine
Animals
Urinary Bladder, Neurogenic
Isovolumetric contraction
Cyclic Nucleotide Phosphodiesterases, Type 5
030219 obstetrics & reproductive medicine
business.industry
Therapeutic effect
Phosphodiesterase 5 Inhibitors
medicine.disease
Rats
Peripheral
Atropine
cGMP-specific phosphodiesterase type 5
Crush injury
Female
Neurology (clinical)
business
Perfusion
medicine.drug
Subjects
Details
- ISSN :
- 15206777 and 07332467
- Volume :
- 39
- Database :
- OpenAIRE
- Journal :
- Neurourology and Urodynamics
- Accession number :
- edsair.doi.dedup.....bac021ad98060bde414cbda97c59c4fe