MP31-06 UPREGULATION OF PHOSPHODIESTERASE TYPE 5 IN THE HYPERPLASTIC PROSTATE: A RAT MODEL STUDY

Abstract

You have accessJournal of UrologyBenign Prostatic Hyperplasia: Basic Research1 Apr 2015MP31-06 UPREGULATION OF PHOSPHODIESTERASE TYPE 5 IN THE HYPERPLASTIC PROSTATE: A RAT MODEL STUDY Wenhao Zhang, Ping Chen, Devendra Singh Negi, Zhuo Li, Keke Zhao, Qi Mao, and Xinhua Zhang Wenhao ZhangWenhao Zhang More articles by this author , Ping ChenPing Chen More articles by this author , Devendra Singh NegiDevendra Singh Negi More articles by this author , Zhuo LiZhuo Li More articles by this author , Keke ZhaoKeke Zhao More articles by this author , Qi MaoQi Mao More articles by this author , and Xinhua ZhangXinhua Zhang More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2015.02.1361AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Both erectile dysfunction (ED) and lower urinary tract symptoms (LUTS)/ benign prostatic hyperplasia (BPH) are quite common for aging males. Phosphodiesterase type 5 inhibitors (PDE5-Is) have been proven as an effective pharmacotherapy for men suffering from ED. Numerous clinical trials have also confirmed the efficacy of PDE5-Is for LUTS/BPH, while tadalafil was recently licensed in USA and in European Union for treating LUTS/BPH with or without ED. However, the mechanisms of PDE5-Is in treating LUTS/BPH are still unclear. In this study we developed a rat model of BPH and the major contraction and relaxation molecules in the prostate were investigated with phosphodiesterase type 5 (PDE5) emphasized. METHODS 250g-300g male Wistar rats were divided into two groups: group 1 (n=16) was treated with 0.1 ml sesame oil; group 2 (n=16) was treated with subcutaneous injection of testosterone propionate (TP) (2 mg/d) for 30 days. Rats were weighed and sacrificed under anesthesia on day 31. The whole ventral prostatic lobes were quickly removed and weighed. PDE5, nitric oxide synthase isoforms (nNOS and eNOS) and adrenoreceptor subtypes (α1a,α1b and α1d) were determined with real time RT-PCR. PDE5 was further analyzed with western-blot and histological examination. Serum testosterone (T) was measured with ELISA. RESULTS BPH model was validated with significantly enlarged prostate and H-E stain. BPH rats group also showed a significant increased serum T level. PDE5 localized mainly in fibromuscular stroma cells as well as in endothelial and smooth muscle cells of blood vessels in prostate. BPH upregulated PDE5 expression by two fold at the gene level and approximately threefold at transcriptional level. Real time RT-PCR also showed that α1a, α1d and nNOS were augmented significantly in BPH group but with no change in the level of eNOS and α1b between BPH and control group. CONCLUSIONS Our novel data showed a higher expression of PDE5 in the BPH group than in controls. The increased expression of PDE5 mRNA and protein in BPH rat prostate could explain the effectiveness and possible mechanism of PDE5-Is in treating LUTS/BPH. Fibromuscular stroma cells as well as endothelial and smooth muscle cells of blood vessels could be the main target tissue of PDE5-Is in the prostate. However, further functional studies are required. © 2015 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 193Issue 4SApril 2015Page: e357 Advertisement Copyright & Permissions© 2015 by American Urological Association Education and Research, Inc.MetricsAuthor Information Wenhao Zhang More articles by this author Ping Chen More articles by this author Devendra Singh Negi More articles by this author Zhuo Li More articles by this author Keke Zhao More articles by this author Qi Mao More articles by this author Xinhua Zhang More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...