Sildenafil Citrate-Restored eNOS and PDE5 Regulation in Sickle Cell Mouse Penis Prevents Priapism Via Control of Oxidative/Nitrosative Stress

Trinity Bivalacqua, Biljana Musicki, Lewis L. Hsu, Dan E Berkowitz, Hunter C. Champion, Arthur Burnett

Research output: Contribution to journalArticle

Abstract

Sildenafil citrate revolutionized the practice of sexual medicine upon its federal regulatory agency approval approximately 15 years ago as the prototypical phosphodiesterase type 5 inhibitor indicated for the treatment of male erectile dysfunction. We now provide scientific support for its alternative use in the management of priapism, a clinical disorder of prolonged and uncontrolled penile erection. Sildenafil administered continuously to sickle cell mice, which show a priapism phenotype, reverses oxidative/nitrosative stress effects in the penis, mainly via reversion of uncoupled endothelial nitric oxide synthase to the functional coupled state of the enzyme, which in turn corrects aberrant signaling and function of the nitric oxide/cyclic GMP/protein kinase G/phosphodiesterase type 5 cascade. Priapism tendencies in these mice are reverted partially toward normal neurostimulated erection frequencies and durations after sildenafil treatment in association with normalized cyclic GMP concentration, protein kinase G activity and phosphodiesterase type 5 activity in the penis. Thus, sildenafil exerts pleiotropic effects in the penis that extend to diverse erection disorders.

Original languageEnglish (US)
Article numbere68028
JournalPLoS One
Volume8
Issue number7
DOIs
StatePublished - Jul 2 2013

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Priapism
Oxidative stress
penis
Penis
cGMP-dependent protein kinase
citrates
cyclic GMP
Oxidative Stress
oxidative stress
Type 5 Cyclic Nucleotide Phosphodiesterases
Cyclic GMP-Dependent Protein Kinases
Cyclic GMP
mice
Guanylate Kinases
cells
Penile Erection
Phosphodiesterase 5 Inhibitors
nitric oxide
Nitric Oxide Synthase Type III
medicine

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Sildenafil Citrate-Restored eNOS and PDE5 Regulation in Sickle Cell Mouse Penis Prevents Priapism Via Control of Oxidative/Nitrosative Stress. / Bivalacqua, Trinity; Musicki, Biljana; Hsu, Lewis L.; Berkowitz, Dan E; Champion, Hunter C.; Burnett, Arthur.

In: PLoS One, Vol. 8, No. 7, e68028, 02.07.2013.

Research output: Contribution to journalArticle

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