Phosphodiesterase type 5 inhibitor attenuates chronic ischemia-induced prostatic hyperplasia in a rat model

Prostate. 2019 Apr;79(5):536-543. doi: 10.1002/pros.23759. Epub 2018 Dec 28.

Abstract

Background: Many elderly men suffer from benign prostatic hyperplasia (BPH). Recently, chronic ischemia in the prostate has been suggested to be related to BPH. Thus, the impact of chronic ischemia on the development of prostatic hyperplasia and the efficacy of phosphodiesterase type 5 (PDE5) inhibitor for hyperplasia were evaluated in a rat model with chronic ischemia induced by local atherosclerosis.

Methods: Eighteen male Sprague-Dawley rats were divided into three groups: sham operation, regular diet, placebo (SRP); arterial endothelial injury, high cholesterol diet, placebo (AHP); or arterial endothelial injury, high cholesterol diet, and tadalafil as a PDE5 inhibitor (AHT). The endothelial injury in the common iliac arteries was performed using a 2-Fr Fogarty arterial embolectomy catheter through an incision in the femoral artery into the common iliac artery. Diet and oral drugs were administrated for 8 weeks after surgery. At 8 weeks, blood flow to the ventral prostate (VP) was measured using laser speckle blood flow analysis, and the VP was histologically evaluated.

Results: In the AHP group, prostatic blood flow was reduced, and mean VP weight and the interstitial area were significantly enlarged compared with the SRP group. In the AHT group, tadalafil administration obviously ameliorated the reduction of prostatic blood flow relative to the AHP group. Importantly, mean VP weight and the morphological changes in the AHT group were significantly smaller than those in the AHP group.

Conclusions: Enlargement of the VP resulted from chronic ischemia induced by local arteriosclerosis. Also, administration of tadalafil attenuated VP enlargement. Chronic ischemia in the prostate might thus contribute to the development of BPH, and PDE5 inhibitors might provide an innovative approach to preventing BPH.

Keywords: PDE5 inhibitor; atherosclerosis; chronic ischemia; prostatic hyperplasia.

MeSH terms

  • Animals
  • Disease Models, Animal
  • Ischemia / complications*
  • Ischemia / drug therapy
  • Ischemia / pathology
  • Male
  • Phosphodiesterase 5 Inhibitors / pharmacology*
  • Prostate / blood supply*
  • Prostate / pathology
  • Prostatic Hyperplasia / drug therapy*
  • Prostatic Hyperplasia / etiology*
  • Prostatic Hyperplasia / pathology
  • Rats
  • Rats, Sprague-Dawley
  • Tadalafil / pharmacology

Substances

  • Phosphodiesterase 5 Inhibitors
  • Tadalafil