A role for phosphodiesterase type 5 inhibitors in remodelling the urinary bladder after radiation exposure

PLoS One. 2020 Nov 9;15(11):e0242006. doi: 10.1371/journal.pone.0242006. eCollection 2020.

Abstract

Minimizing the toxicity of radiotherapy is challenging. We investigated the effects of a phosphodiesterase type-5 inhibitor (PDE5I) on the urinary bladder after pelvic radiotherapy. Eight rats were assigned to each group (group 1: control; group 2: radiation; group 3: radiation plus PDE5I). Radiation dose was 10 Gy/one fraction. Udenafil (20 mg/kg, daily for 4 weeks) was administered in group 3. Cystometry was performed 4 weeks after treatment, followed by real-time PCR for PDE5, vascular endothelial growth factor (VEGF), and endothelial nitric oxide synthase (eNOS) mRNA, western blotting for PDE5, cyclic GMP-dependent protein kinase (PRKG), VEGF164, Akt, eNOS and NADPH oxidase (NOX)-2 proteins, and immunohistochemistry for eNOS. The expression of both VEGF mRNA and eNOS mRNA was higher in group 3 than in group 2. VEGF and eNOS protein expression improved with PDE5I treatment. Akt protein phosphorylation was higher in group 3 than in group 2, but NOX-2 protein expression was lower in group 3 than in group 2. Immunohistochemistry showed that the mean density of arterioles expressing eNOS was higher in group 3 than in group 2. Cystometry revealed that the intercontraction interval was remarkably longer in group 3 than in group 2 but that the maximal voiding pressure was higher in group 2 than in group 3. Daily treatment with a PDE5I after radiotherapy may prevent bladder storage dysfunction, potentially due to its effects on vasodilation and angiogenesis and through minimizing tissue oxidative damage by means of the VEGF/Akt/eNOS pathway.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Male
  • Pelvis / radiation effects
  • Phosphodiesterase 5 Inhibitors / therapeutic use*
  • Prostatic Neoplasms / radiotherapy
  • Radiation Exposure / adverse effects*
  • Rats, Wistar
  • Urinary Bladder / drug effects*
  • Urinary Bladder / pathology
  • Urinary Bladder / radiation effects*

Substances

  • Phosphodiesterase 5 Inhibitors

Grants and funding

Initials of the authors who received each award: DSL Grant numbers awarded to each author: none The full name of each funder: Dong-a ST Co., Ltd. (Seoul, Republic of Korea) URL of each funder website: http://www.donga-st.com/Main.da Did the sponsors or funders play any role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript?: NO The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.