Tadalafil, a phosphodiesterase type 5 inhibitor, improves bladder blood supply and restores the initial phase of lower urinary tract dysfunction in diabetic rats

Neurourol Urodyn. 2018 Feb;37(2):666-672. doi: 10.1002/nau.23372. Epub 2017 Aug 7.

Abstract

Aims: To investigate the effect of tadalafil on bladder blood flow and lower urinary tract function in a rat model of diabetes.

Materials and methods: We studied female Sprague-Dawley rats and induced diabetes in some using a single intraperitoneal injection of streptozotocin. We divided the rats into nondiabetes (ND), diabetes (D), and diabetes with tadalafil (DT) groups. The rats were raised for an additional 7 weeks after diabetes induction. The DT group received oral tadalafil (2 mg/kg/day) for 7 days before the experiments. At 7 weeks after diabetes induction, we performed cystometry, resected the bladders for immunohistochemistry (hypoxia-inducible factor-1α [HIF-1α] and 8-oxo-2'-deoxyguanosine [8-OHdG] staining), and measured bladder blood supply using a laser blood flow meter.

Results: The opening pressure, when the urethra opens and urine flow starts, was significantly lower in the DT group than in the D group (24.9 ± 5.9 vs 43.6 ± 12.3 cmH2 O). The inter-contraction interval was significantly longer in the D group than in the ND and DT groups (1566.2 ± 168.7 vs 702.9 ± 165.2 and 787.4 ± 148.8 s). Immunohistochemistry showed positive staining of the urothelial layer for both HIF-1α and 8-OHdG in the D group, but not in the ND or DT groups. Bladder blood flow was significantly lower in the D group than in the ND or DT groups.

Conclusions: Tadalafil improves bladder blood supply and lower urinary tract function in diabetic rats. Tadalafil may be a promising drug that restores lower urinary tract dysfunction in the early phase of diabetes.

Keywords: ischemia; bladder; phosphodiesterase 5; rat.

MeSH terms

  • Animals
  • Diabetes Mellitus, Experimental / physiopathology*
  • Female
  • Lower Urinary Tract Symptoms / drug therapy*
  • Lower Urinary Tract Symptoms / physiopathology
  • Phosphodiesterase 5 Inhibitors / pharmacology*
  • Phosphodiesterase 5 Inhibitors / therapeutic use
  • Rats
  • Rats, Sprague-Dawley
  • Tadalafil / pharmacology*
  • Tadalafil / therapeutic use
  • Urethra / drug effects*
  • Urethra / physiopathology
  • Urinary Bladder / blood supply
  • Urinary Bladder / drug effects*
  • Urinary Bladder / physiopathology

Substances

  • Phosphodiesterase 5 Inhibitors
  • Tadalafil