ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

Endocrine Abstracts (2012) 29 P1050

Phosphodiesterase type 5 expression in human and rat lower urinary tract tissues and the effect of tadalafil on prostate gland oxygenation in spontaneously hypertensive rats

A. Morelli, E. Sarchielli, P. Comeglio, S. Filippi, R. Mancina, M. Gacci, L. Vignozzi, M. Carini, G. Vannelli & M. Maggi

University of Florence, Florence, Italy.

Introduction: In humans, prostate PDE5 expression was prominently localized in the endothelial and smooth muscle cells of the vascular bed, suggesting a possible action of PDE5 inhibitors on prostate blood flow.

Aim: To investigate PDE5 expression in human and rat lower urinary tract (LUT) tissues and determine the effects of PDE5 inhibition with tadalafil on prostatic blood perfusion.

Main outcome measures: Human vesicular-deferential arteries (which originate from the inferior vesical artery) were analyzed for PDE5 expression and activity. The effects of tadalafil on prostate oxygenation were studied in spontaneously hypertensive rats (SHR), characterized by ischemia/hypoxia of the genitourinary tract.

Methods: PDE5 expression was evaluated by quantitative reverse transcription-polymerase chain reaction and immunohistochemistry. SHR were treated with tadalafil (2 mg/kg per day) for 1, 7, or 28 days and compared with untreated SHR and the unaffected counterpart Wistar–Kyoto (WKY) rats. Prostate oxygenation was detected by hypoxyprobe-1 and hypoxia markers (hypoxia-inducible factor-1α (HIF-1α) and endothelin-1 type B (ETB)) immunostaining.

Results: Human vesicular-deferential artery expressed high levels of PDE5, similar to corpora cavernosa, immunolocalized in the endothelial and smooth muscle layer. In these arteries, tadalafil inhibited cGMP breakdown (half maximal inhibitory concentration in the low nanomolar range, as in corpora cavernosa) and increased the relaxant response to sodium nitroprusside. SHR prostate resulted markedly hypoxic (hypoxyprobe immunopositivity) and positive for HIF-1α and ETB, while tadalafil treatment restored oxygenation to WKY level at each time point. The mRNA expression of the HIF-1α target gene, BCL2/adenovirus E1B 19 kDa interacting protein 3, was significantly increased in SHR prostate and partially restored to WKY level by tadalafil.

Conclusion: Human vesicular-deferential artery is characterized by a high expression and activity of PDE5, which was inhibited by tadalafil in vitro. In SHR, tadalafil increases prostate tissue oxygenation, thus suggesting a possible mechanism through which PDE5i exert beneficial effects on LUT symptoms.

Declaration of interest: The authors declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research project.

Funding: This research did not receive any specific grant from any funding agency in the public, commercial or not-for-profit sector.