Ssi prize essay for male erectile dysfunction—research ‘sildenafil causes a dose- and time-dependent downregulation of phosphodiesterase type 6 expression in the rat retina‘

C. M. Gonzalez*, T. Bervig, C. Podlasek, C. F. Huang, K. E. McKenna, K. T. McVary

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

9 Scopus citations

Abstract

Objectives: Some authors have advocated the daily use of sildenafil for prophylaxis against, or treatment of, erectile dysfunction. However, no information has been published to support such a dosage regimen. The safety profile of uninterrupted use of sildenafil has not been evaluated as it pertains to alteration of PDE type 6 in the retina. In the present study we investigated whether short- or long-term exposure to a variety of sildenafil doses affect the expression of an enzyme important in the normal phototransduction cascade.Methods: Sustained-release sildenafil pellets were implanted in 120-day-old male rats with concentrations from 1–200 mg. Rat retinal tissue was harvested 7, 14, and 29 days after implantation. Quantitative reverse transcriptase-polymerase chain reaction (RT-PCR) using GAPDH as an endogenous internal standard was used to quantitate PDE type 6 gene expression.Results: Expression of PDE type 6 was upregulated after 7 days with dosages ≤5 mg (P<0.02). Significant downregulation of PDE type 6 expression was first noted with high dose sildenafil 14 days after implantation (P<0.02). Expression of PDE type 6 was significantly and profoundly downregulated 29 days after implantation for all pellet formulations ≥10 mg (P<0.01).Conclusions: Sildenafil downregulates PDE type 6 expression in a dose- and time-dependent fashion. These findings support the explanation that PDE type 6 inhibition causes the dose-dependent clinical effects of visual disturbance in men taking sildenafil. Implications for long-term, daily use of sildenafil in men are not clear.

Original languageEnglish (US)
Pages (from-to)S9-S14
JournalInternational Journal of Impotence Research
Volume11
DOIs
StatePublished - Sep 1999

Keywords

  • Downregulation
  • Pde6
  • Retina
  • Sildenafil

ASJC Scopus subject areas

  • Urology

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