Effect of sildenafil in the prostate morphology in an animal model of benign prostatic hyperplasia.

Abstract

Introduction & ObjectiveThe Benign Prostatic Hyperplasia (BPH) is a progressive disease characterized by prostatic enlargement, caused by increased cellular proliferation and/or decreased apoptosis. This cellular imbalance leads to prostatic morphological alterations with consequent clinical manifestations. Fosfodiesterase‐5 inhibitors have been recently recommended for treating BPH and its symptoms. It is thought that these drugs promotes a relaxation of smooth muscle of lower urinary organs, improving the voiding symptoms. However the effect of this class of drug on prostatic morphology has not been described yet. Thus, the objective of this study was to investigate if sildenafil would ameliorate morphological modifications in a rodent model of BPH.Material and MethodsWe used 20 SHR (which is described as the best animal model for studying BPH) and 10 Wistar Kyoto (WKY) rats, aged 4 months, divided into 3 groups: Group W (WKY control normotensive rats, n=10); Group H (hypertensive animals without treatment, n=10) and Group HS (hypertensive animals which received sildenafil, n=10). The animals of groups W and H received 3 ml of water daily by gavage. Animals of group HS received sildenafil citrate (1 mg/kg) diluted in 3 ml of water daily by gavage. All groups received the treatments during 40 days in which blood pressure was measured weekly by tail‐cuff plethysmography. The animals were killed by anesthetic overdose and fragments of the ventral prostate were collected. These samples were fixed in buffered formaldehyde and processed for histochemical and immunohistochemical techniques. Morphometric analyses were performed for obtaining the following parameters: Prostatic epithelium height (μm), Collagen area density (%), Smooth muscle area density (%) and Proliferating cells area density (%). All results were expressed as mean ± SD. Statistical analyzes were performed using ANOVA followed by Bonferroni's post‐test.ResultsAs expected, animals from groups H and HS presented a higher arterial pressure when compared to group W during all the experiment. The epithelium of hypertensive animals were 41% increased in comparison to control animals, what confirms these animals as an experimental model of BPH. The sildenafil treatment was effective in decreasing the epithelial height to normal values. The analysis of collagen area density did not pointed differences among the three studied groups. Nevertheless, the smooth muscle area density was greatly augmented by 98% in H group compared to controls. Again, the sildenafil treatment restored normal values for this parameter. Despite these positive effects of sildenafil on prostate morphology, regarding the proliferating cells area density, sildenafil did not prevent the augmented values observed in the hypertensive model of BPH.ConclusionThe SHR present some morphological alterations of prostate which is compatible to BPH. Sildenafil somehow acts in prostate morphology, restoring the normal aspect in some parameters.Support or Funding InformationValença Medical School, FAPERJ, CNPq, and CAPESThis abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.